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YEAR 1 - Organisation of the Body (Anton) > 14. Endocrinology (HT) > Flashcards

14. Endocrinology (HT) Flashcards

1
Q

Give some examples of some hormones that involve a GPCR response.

A
  • Protein hormones (e.g. glucagon)
  • Amines (e.g. adrenaline)
  • Lipids (e.g. prostaglandins)
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2
Q

Can a single hormones activate multiple GPCR types?

A

Yes

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3
Q

State what mechanism each GPCR works by.

A
  • Gq - Activates phospholipase C (PLC)
  • Gi - Inhibits adenylate cyclase (AC) activity and therefore the production of cAMP from ATP
  • Gs - Stimulates adenylate cyclase activity
  • G12/13 - Rho family
  • Gβ - Activates inwardly-rectifying potassium channels
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4
Q

What type of receptor is the insulin receptor and what mechanism does it work by?

A
  • Enzyme-linked
  • Binding causes tyrosine kinase activation, leading to autophosphorylation of the receptor and the insertion of GLUT4 into the membrane
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5
Q

Draw the structure of a steroid receptor (type IV, intracellular receptor).

A
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6
Q

What are some ways in which a hormone signal is turned off?

A
  • Removal or degradation of the hormone
  • Desensitisation of the receptor
  • Internalisation of the receptor
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7
Q

What is receptor desensitisation?

A

The decreased responsiveness that occurs with repeated or chronic exposure to an agonist.

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8
Q

Describe the mechanisms involved in the desensitisation and resensitisation of a GPCR.

A
  • Desensitisation occurs by the phosphorylation of the receptor by GRK (G-protein receptor kinase)
  • This then recruits arrestin, which prevents G-protein interaction, blocking the downstream effects of the receptor
  • Resensitisation involves dephosphorylation of the receptor
  • Desensitisation may also happen by endocytosis of the receptor (which can be dependent or independent of the arrestin)
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9
Q

How are the insulin and glucagon receptor pathways integrated?

A
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10
Q

What are some effects that disease can have on hormone receptors?

A
  • Failure of ligand binding
  • Failure of signal transduction
  • Constitutively active receptor systems
  • Antibodies to receptor
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11
Q

What are the two types of receptor mutations?

A
  • Inactivating -> Receptor does not function despite hormone present
  • Activating -> Receptor continually active without hormone bound
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12
Q

What is the endocrine system?

A

One of the major control systems that use chemical messengers (the other is the nervous system).

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13
Q

What is a hormone?

A

A chemical messenger released from an endocrine cell to influence the activity of another/the same cell via a receptor.

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14
Q

At what order of concentration are endocrine hormones typically present in blood?

A

10-7 to 10-13 M

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15
Q

Is hormone concentration the only way of regulating the response to the hormone?

A

No, the receptors may also be controlled to determine sensitivity.

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16
Q

Define an endocrine gland.

A

A well-defined collection of endocrine cells.

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17
Q

Define a diffuse endocrine system.

A

Many hormone-producing cells not aggregated in a gland, but dispersed (e.g. in the gut).

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18
Q

Define a neuroendocrine system.

A

Neurons releasing hormones both into the blood stream and in the CNS.

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19
Q

Show the different routes of endocrine communiaction affecting cells.

A
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20
Q

What is neuroendocrine hormone action?

A

The hormone is released from a neuron into the blood stream.

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21
Q

What is paracrine hormone action?

A

The hormone acts on local cells via the extracellular fluid.

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22
Q

What is autocrine hormone action?

A

The hormone acts on the cell producing the hormone.

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23
Q

What are the functions of the endocrine system?

A

The endocrine system promotes survival of the species by:

  • Promoting survival of the individual
    • Effects on development, growth and differentiation
    • Homeostasis (NOTE: this is often disturbed short-term for long-term gain) -> Including anticipatory responses
    • Response to an altered external environment - especially emergency ‘stress responses’
  • Control of the processes involved in reproduction
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24
Q

What does the speed and duration of endocrine action depend on?

A
  • Rapidity of release
  • Half-life of hormone
  • Rapidity of action
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25
Q

Give an example of hormone action that is:

  • Fast
  • Intermediate
  • Slow
A
  • Fast -> Adrenaline in stress
  • Intermediate -> Insulin in response to meal
  • Slow -> Cortisol in lung development
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26
Q

What are the two divisions of hormone effects on a cell?

A
  • Activational - Effects that disappear when the hormone is removed.
  • Organisational - Effects that cause a permanent change in the behaviour of their target cells.
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27
Q

Describe some of the control of the release, synthesis and release of hormones.

A
  • Inputs: can be direct or indirect.
  • Central integration: The central nervous system (CNS) integrates endocrine control via the pituitary gland and peripheral endocrine systems.
  • Output: the release of defined amounts of hormone in a certain temporal pattern allows both amplitude and frequency modulation.
  • Feed-forward control: e.g. from hypothalamus to pituitary to endocrine organ to target organ.
  • Feed-back control (usually negative) by either hormones or their effects - a homeostatic mechanism. This implies a certain “normal level” of hormone in plasma when ‘at rest’.
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28
Q

Explain (using examples) the secretion of hormones in pulses and according to rhythms.

A
  • Hormones are released in pulses, which show up as peaks in a graph of hormone concentration against time
  • These pulses vary during the day according to rhythms, including diurnal and reproductive rhythms
  • For example, ACTH (and therefore cortisol) has a very high peak in the release in the morning, to prepare the person for the day
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29
Q

What are the two types of hormone rhythm you need to know about?

A
  • Diurnal
  • Reproductive (e.g. menstruation?)
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30
Q

What is a diurnal rhythm?

A

A biological rhythm that is synchronized with the day/night cycle. It may or may not be a circadian rhythm.

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31
Q

What is the clinical relevance of diurnal hormone rhythms?

A

Comparative blood tests need to be taken at the same time on different days.

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32
Q

Describe where feed-forward control occurs in the endocrine system.

A

From the hypothalamus to pituitary to endocrine organ to target organ.

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33
Q

Describe where feed-back control occurs in the endocrine system.

A
  • By either hormones or their effects
  • Usually negatively effect the hypothalamus and anterior pituitary
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34
Q

What are the different chemical types of hormone? Give examples of each.

A

Synthesised and stored in endocrine glands:

  • Protein
  • Peptide
  • Bioactive amine
  • Steroid
  • Thyroid

Hormones produced enzymatically as they are needed:

  • Gaseous mediators
  • Prostaglandins
  • Angiotensin II
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35
Q

Categorise the different types of hormone based on whether they are hydrophilic or hydrophobic. What is the importance of this?

A

Hydrophobic:

  • Steroids
  • Prostaglandins

Hydrophilic:

  • Peptide, polypeptide, protein, glycoprotein

Both hydrophilic and hydrophobic properties, very small:

  • Catecholamines
  • Thyroid hormones
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36
Q

Give an example of each of these type of hormone:

  • Bioactive amine
  • Polypeptide
  • Protein
  • Glycoprotein
  • Steroid
  • Prostaglandin
  • Gaseous mediators
A
  • Bioactive amine -> T3, Catecholamines
  • Polypeptide -> Insulin
  • Protein -> Prolactin
  • Glycoprotein -> Luteinising hormone
  • Steroid -> Testosterone
  • Prostaglandin -> Prostaglandin E2
  • Gaseous mediators -> NO
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37
Q

Describe the range in sizes of the different endocrine hormones.

A
  • Amines, thyroid hormones, steroids and some peptides are very small.
  • Many polypeptide, protein and glycoprotein hormones are very large.
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38
Q

What is constitutive and regulated secretion?

A
  • Constitutive secretion -> Secretion straight away
  • Regulated secretion -> Secretion in a controlled way
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39
Q

Describe the biosynthesis of proteins, polypeptides and glycopeptides.

A
  • Translated on the rough endoplasmic reticulum
  • Secreted by either the regulated pathway (e.g. insulin, prolactin) or the constitutive pathway (cytokines, growth factors)
  • The original translation product (the prohormone) is usually processed proteolytically to yield the active hormone
  • Many endocrine cells produce more than one active peptide hormone, in varying amounts. These may be derived) from the same prohormone or from different prohormones.
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40
Q

Describe the biosynthesis of steroid hormones.

A

Synthesized rapidly on demand from cholesterol via enzymes in the mitochondria and smooth endoplasmic reticulum.

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41
Q

Describe the biosynthesis of bioactive amines.

A

Produced from tyrosine via intracellular enzymes

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42
Q

Describe the biosynthesis of thyroid hormones.

A

Iodothyronines are produced by iodination and coupling of tyrosyl residues in a protein (thyroglobulin) which are then released by proteolysis (see Thyroid lecture).

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43
Q

Describe the biosynthesis of angiotensin II.

A

Produced by conversion of plasma angiotensin I by angiotensin-converting enzyme in the lung.

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44
Q

Describe the biosynthesis of NO.

A

Produced from arginine by the intracellular enzyme nitric oxide synthase .

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45
Q

Describe the biosynthesis of prostaglandins.

A

Synthesized rapidly on demand from arachidonic acid via the intracellular cyclooxygenase enzymes.

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46
Q

Describe the storage of the different types of hormone in endocrine cells.

A
  • Amines and many peptides -> Stored in large amounts in intracellular granules. Some peptides (e.g. growth factors) are not stored but released as they are made.
  • Steroids, prostaglandins, gases -> Not stored
  • Large amounts of iodinated thyroglobulin, the precursor for thyroid hormone synthesis, but not the free hormone, are stored in the thyroid follicles. However the blood contains a large reservoir of protein-bound thyroid hormone.
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47
Q

Describe the order of the normal concentrations of the endocrine hormones in plasma.

A
  • Protein and polypeptide hormones -> Nanomolar concentrations in plasma
  • Steroid hormones -> Sub-micromolar concentrations, mostly bound to specific proteins
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48
Q

Are endocrine hormones in the blood transported freely?

A
  • Hydrophilic peptide/protein and amine hormones can circulate freely in plasma.
  • Most steroid and thyroid hormones are substantially bound to specific binding proteins in the plasma so there is an equilibrium between bound and free.
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49
Q

What is the effect of endocrine hormones binding to plasma proteins?

A

Binding of hormones to proteins in the plasma substantially reduces their clearance and thus extends their ‘half-life’.

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50
Q

Describe the metabolism and excretion of endocrine hormones.

A
  • Hormones have a variable half-life, but most are deactivated rapidly. The first step in their metabolism generally destroys their activity.
  • Hormones that are internalized with their receptor are usually degraded in the lysosomes of the target cells.
  • Steroid hormones are degraded in the liver (and in target tissues).
  • Hormones are also lost by excretion: through the kidneys (water soluble), liver and bile.
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51
Q

How are endocrine hormone levels in plasma measured?

A

Most are measured by some form of binding assay: most common is the radioimmunoassay.

(These must however be validated by a bioassay to ensure they measure active hormone).

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52
Q

Describe the types of endocrine pathologies and how they are caused.

A

Defects can involve:

  • Production of hormone
  • Release of hormone
  • Mechanism of action

Caused by:

  • Genetic factors
  • Tumours
  • Autoimmune disease
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53
Q

For any particular hormone, what do you need to know?

A
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54
Q

Remember to add flashcards about the structure of cells that synthesise and store endocrine hormones.

A

Do it.

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55
Q

What germ layer does the pancreas derive from?

A

Endoderm

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56
Q

Draw the gross and histological structure of the pancreas.

A
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57
Q

What percentage of the pancreas do the Islets of Langerhans make up?

A

1% - The rest of the pancreas has a moslty exocrine role.

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58
Q

From when are Islets of Langerhans distinguishable histologically in the pancreas?

A

From 12th week of gestation

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59
Q

How many cells are in an Islet of Langerhans?

A

Around 1000

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60
Q

How many Islets of Langerhans in the pancreas are there?

A

Around 1,000,000

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61
Q

What are the different cell types in the Islets of Langerhans and what hormone does each secrete?

A
  • α-cells -> Glucagon
  • β-cells -> Insulin
  • δ-cells -> Somatostatin

Also:

  • PP-cells -> Pancreatic polypeptide (PP)
  • ε-cells -> Ghrelin
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62
Q

Label this.

A
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63
Q

In Islets of Langerhans, what are the percentages of the different cell types?

A
  • β-cells (insulin) -> 55%
  • α-cells (glucagon) -> 38%
  • δ-cells (somatostatin) -> Less than 5%
  • PP-cells (pancreatic polypeptide) -> 1%
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64
Q

On what chromosome is the insulin gene located?

A

11

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65
Q

Which cells produce insulin?

A

β-cells in the Islets of Langerhans in the pancreas

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66
Q

How is mature insulin stored in β-cells?

A

In secretory vesicles

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67
Q

How many insulin granules are there in a β-cell and how much insulin does each contain?

A
  • 10,000 secretory granules per β-cell
  • Each contains 8 femtograms of insulin
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68
Q

Show how glucose sensing works in β-cells of the pancreas. [EXTRA]

A
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69
Q

Is insulin secretion happen all in one go?

A

No, it is biphasic.

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70
Q

What are some things that stimulate and inhibit insulin secretion?

A

Stimulated by:

  • Glucose
  • Amino acids
  • Fatty acids
  • Parasympathetic innervation
  • Hormones:
    • GLP (glucagon-like peptide)
    • Glucagon (counter-intuitive)

Inhibited by:

  • Sympathetic innervation
  • Hormones:
    • Somatostain (from δ-cells)
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71
Q

What are the main metabolic effects of insulin?

A

On carbohydrates:

  • Increased GLUT4 mediated glucose uptake (muscle and adipose)
  • Stimulates glycolysis
  • Stimulates glycogenesis (liver major store of glycogen)
  • Inhibits gluconeogenesis (liver)
  • Inhibits glycogenolysis
  • Inhibits glucagon production by α-cells (paracrine)

On proteins:

  • Stimulates amino acid uptake
  • Stimulates protein synthesis

On lipids:

  • Stimulates lipogenesis
  • Inhibits lipolysis
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72
Q

Draw the mechanism of action of insulin in target tissues.

A
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73
Q

Compare and explain the insulin response to oral and intravenous glucose.

A

The incretin effect: When the glucose is taken orally, incretin hormones (such as GLP, glucagon-like peptide) are released in response to the nutrients in the GI tract. This results in a higher insulin spike.

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74
Q

What are the effects of glucagon-like peptide (GLP)? [IMPORTANT]

A
  • Stimulates insulin secretion
  • Inhibits glucagon secretion
  • Inhibits appetite
  • Inhibits gastric emptying
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75
Q

What is the effect of incretin hormones (such as GLP) on beta-cells in the pancreas?

A

Increase insulin secretion via the GLP1 receptor (Gαs-coupled GPCR).

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76
Q

For insulin, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Protein
    • Two peptide chains referred to as the A chain and B chain, linked by disulfide bonds
  • Site and mechanism of production & release
    • Beta cells of the pancreas
    • Expressed as preproinsulin, then converted to proinsulin, then insulin
  • Stimuli that cause or inhibit its release
    • Stimulated by:
      • Glucose
      • Amino acids
      • Fatty acids
      • Parasympathetic innervation
      • Hormones:
        • GLP (glucagon-like peptide)
        • Glucagon (counter-intuitive)
    • Inhibited by:
      • Sympathetic innervation
      • Hormones:
        • Somatostain (from δ-cells)
  • Pattern of secretion into the blood/extracellular fluid
    • Biphasic
  • Mechanism of transport in the blood/extracellular fluid
    • Freely transported?
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • All cells, especially liver, muscle and fat
    • Binds to a receptor with tyrosine kinase activity, leading to insertion of GLUT4 transporter into the membrane
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Diabetes
    • Hypoglycaemia
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77
Q

What are sulphonylureas?

A

Medications that control blood sugar levels in patients with type 2 diabetes by stimulating the production of insulin in the pancreas and increasing the effectiveness of insulin in the body.

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78
Q

What cells produce glucagon?

A

α-cells in Islets of Langerhans in the pancreas

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79
Q

What chemical class of hormone is glucagon?

A

Polypeptide

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80
Q

Describe how glucagon is synthesised.

A

Just like insulin, it is synthesised as preproglucagon, then converted to proglucagon and then finally to glucagon.

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81
Q

What are some things that stimulate and inhibit glucagon secretion?

A

Stimulated by:

  • Hypoglycaemia
  • Sympathetic innervation
  • Specific amino acids
  • Gastrointestinal hormones

Inhibited by:

  • Somatostatin
  • Insulin (paracrine)
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82
Q

What are the main metabolic effects of glucagon?

A

Promotes glycogenolysis, gluconeogenesis and lipolysis.

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83
Q

Describe the mechanism of action of glucagon on target cells.

A
  • Glucagon receptors are Gs-coupled GPCRs
  • Mechanism of action involves adenylate cyclase activity and increased [cAMP] and subsequent PKA phosphorylation
  • Affects both gene expression and post-translational modifications (signalling).
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84
Q

What are the main sites of action of glucagon?

A
  • Muscle
  • Liver
  • Adipose
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85
Q

For glucagon, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide hormone
  • Site and mechanism of production & release
    • Alpha cells of the pancreas
  • Stimuli that cause or inhibit its release
    • Stimulated by:
      • Hypoglycaemia
      • Sympathetic innervation
      • Specific amino acids
      • Gastrointestinal hormones
    • Inhibited by:
      • Somatostatin
      • Insulin (paracrine)
  • Pattern of secretion into the blood/extracellular fluid
    • ???
  • Mechanism of transport in the blood/extracellular fluid
    • Transported freely in blood?
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Muscle, liver and fat cells
    • Glucagon receptors are Gs-coupled GPCRs
    • Mechanism of action involves adenylate cyclase activity and increased [cAMP] and subsequent PKA phosphorylation
    • Affects both gene expression and post-translational modifications (signalling)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Opposite to insulin
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86
Q

What hormones is glucagon synergistic with? [IMPORTANT]

A
  • Catecholamines
  • Glucocorticoids
  • Growth hormone
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87
Q

What cells produce somatostatin?

A
  • δ-cells in Islets of Langerhans in the pancreas
  • Brain
  • GI tract
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88
Q

What chemical class of hormone is somatostatin?

A

Peptide

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89
Q

What is the effect of somatostatin in the pancreas?

A

Paracrine inhibitor of insulin and glucagon secretion (i.e. it is a brake on all islet cell activity)

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90
Q

Describe the production of somatostatin.

A

It is a polypeptide cleaved from prosomatostatin

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91
Q

Describe the somatostatin mechanism of action in the pancreas.

A
  • Somatostatin receptor is an inhibitory (Gi-coupled) GPCR.
  • This decreases adenylate cyclase activity and therefore decreases cAMP
  • Decreased cAMP leads to decreased secretion of insulin and glucagon
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92
Q

For somatostatin, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide hormone (paracrine)
    • 28 amino acid molecule (in pancreas)
  • Site and mechanism of production & release
    • Cleaved from prosomatostatin
    • Produced in the pancreatic islets, brain and GI tract
    • Add mechanism of release
  • Stimuli that cause or inhibit its release
    • Add
  • Pattern of secretion into the blood/extracellular fluid
    • Add
  • Mechanism of transport in the blood/extracellular fluid
    • Paracrine hormone
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Inhibits insulin and glucagon release
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Add
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93
Q

What is an insulinoma?

A

A tumor of the pancreas that is derived from beta cells and secretes insulin.

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94
Q

What are the effects of insulinoma?

A
  • Symptoms of hypoglycaemia -> Recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting.
  • Severe hypoglycemia may result in seizures, coma, and permanent neurological damage.
  • Symptoms resulting from the catecholaminergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common.
  • Sudden weight gain is sometimes seen.
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95
Q

What is the ‘master gland’?

A

The pituitary gland -> Because it secretes hormones that act on lots of other organs.

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96
Q

Draw the location of the pituitary gland.

A

Situated beneath the hypothalamus of the brain, in a depression (‘pituitary fossa’) of the skull.

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97
Q

What are the two main parts of the pituitary and what are their proper names?

A
  • Anterior pituitary -> Adenohypophysis
  • Posterior pituitary -> Neurohypophysis

Note: Sometimes people also talk about a small intermdiate lobe between the anterior and posterior. In humans the intermediate love becomes interspersed with the anterior lobe.

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98
Q

Describe the development of the pituitary gland.

A

Anterior:

  • Rathke’s pouch grows up from oropharyngeal ectoderm (roof of the mouth) to form the anterior pituitary.

Posterior:

  • The infundibular process grows down from the forebrain vesicle to form the posterior pituitary.
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99
Q

Which part of the brain is the pituitary gland related to?

A

Hypothalamus

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100
Q

Describe how the pituitary gland is connected with the hypothalamus.

A
  • Anterior pituitary receives hormones from the hypothalamus via portal veins
  • Posterior pituitary is formed by neurosecretory neurons that start in the hypothalamus
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101
Q

Describe the vasculature of the hypothalamus and pituitary.

A
  • Posterior pituitary receives blood supply direct from internal carotid artery
  • Hypothalamus receives branches direct from internal carotid artery -> These form a capillary plexus in the base of the hypothalamus that forms portal veins which supply the anterior pituitary.
  • Anterior pituitary receives blood from hypothalamo-hypophysial portal veins.
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102
Q

How many endocrine cell types are found in the anterior pituitary?

A

5

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103
Q

How can the different endocrine cell types in the anterior pituitary be differentiated?

A

Immunocytochemistry

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104
Q

What are the main endocrine cell types in the anterior pituitary?

A
  • Thyrotrophs
  • Corticotrophs
  • Gonadotrophs
  • Lactotrophs
  • Somatotrophs
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105
Q

Describe the histological structure of the anterior pituitary.

A

The hormones stored in secretory granules.

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106
Q

Describe the different ways in which the activity of the anterior pituitary can be regulated. [IMPORTANT]

A
  • By CNS -> Specific releasing factors from the hypothalamus reach the anterior pituitary via the portal veins
  • Negative feedback by target hormones (at pituitary and hypothalamus)
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107
Q

What are the different types of hormone involved in the hypothalamo-pituitary-endocrine gland axis?

A
  • The hormones from the hypothalamus are called releasing hormones -> e.g. GnRH (gonadotrophin-releasing hormone)
  • The hormones from the pituitary are called trophic hormones -> Secreted by lactoTROPHS, gonadoTROPHS, etc.
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108
Q

Draw the hypothalamus-pituitary-endocrine gland axis, along with the different types of feedback.

A
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109
Q

Name all of the hormones secreted by the anterior pituitary gland.

A
  • TSH -> Thyroid stimulating hormone (a.k.a thyrotrophin)
  • ACTH -> Adrenocorticotrophic hormone
  • LH + FSH -> Luteinising hormone + Follicle-stimulating hormone (a.k.a gonadotrophins)
  • PRL -> Prolactin (a.k.a. mammotrophin)
  • GH -> Growth hormone
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110
Q

By what cells is TSH secreted?

A

Thyrotroph cells (in the anterior pituitary)

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111
Q

Describe the chemical nature of TSH.

A
  • Glycoprotein hormone [IMPORTANT]
  • Made of alpha and beta subunits; the beta subunit is specific to TSH, the alpha subunit is shared with LH and FSH.
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112
Q

Describe the actions of TSH.

A

Acts in the thyroid:

  • Stimulates thyroid hormone (T3 and T4) production + Increases iodine uptake by the thyroid (required for thyroid hormone production)
  • Stimulates thyroid growth
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113
Q

What are the receptors for TSH?

A

G protein coupled to cAMP, on thyroid gland follicular cells.

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114
Q

Describe the control of TSH release. What is it released in response to?

A
  • Stimulated by thyrotrophin releasing hormone (TRH) from the hypothalamus -> Secretion of TRH is stimulated by cold and by stress via the CNS.
  • Inhibited by T3 & T4 (negative feedback)
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115
Q

Describe when TSH is released.

A
  • Released in pulses with a diurnal rhythm.
  • Also released in response to cold and stress.
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116
Q

Draw the structure of the hypothalamic-pituitary-thyroid axis.

A
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117
Q

For TSH, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Glycoprotein
  • Site and mechanism of production & release
    • Released from pituitary gland
  • Stimuli that cause or inhibit its release
    • Released in response to cold and stress also
  • Pattern of secretion into the blood/extracellular fluid
    • Released in pulses in a diurnal rhythmn
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Binds to thyroid cells
    • Acts by increasing intracellular cAMP with G-protein
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Rare
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118
Q

By what cells is ACTH secreted?

A

Corticotroph cells (in the anterior pituitary)

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119
Q

Describe the chemical nature of ACTH.

A

Polypeptide hormone

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120
Q

Describe the actions of ACTH.

A

Acts on the adrenal cortex and stimulates the secretion of:

  • Mostly glucocorticoids (i.e. cortisol)
  • Some increase in sex steroids
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121
Q

What are the receptors for ACTH?

A

G protein coupled to cAMP, on adrenal cortex cells.

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122
Q

Describe the control of ACTH release. What is it released in response to?

A
  • Stimulated by corticotrophin releasing hormone (CRH) from the hypothalamus -> Secretion of CRH is stimulated by stress via the CNS.
  • Inhibited by glucocorticoids like cortisol (negative feedback)
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123
Q

Describe when ACTH is released.

A
  • Released in pulses with a diurnal rhythm -> High at 7am, low at midnight.
  • Also released in response to stress and hypoglycaemia.
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124
Q

From what prohormone is ACTH cleaved? [EXTRA]

A

POMC

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125
Q

Describe some dysfunctions of ACTH.

A
  • Cushing’s disease -> Excess ACTH from corticotrophinoma pituitary tumours, leading to excess glucocorticoid secretion
  • Addison’s disease -> Deficiency of ACTH causes glucocorticoid deficiency
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126
Q

For ACTH, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Polypeptide
  • Site and mechanism of production & release
    • Released from pituitary gland
    • Cleaved from POMC prohormone
  • Stimuli that cause or inhibit its release
    • Released in response to stress and hypoglycaemia
    • Feedback inhibition by glucocorticoids
  • Pattern of secretion into the blood/extracellular fluid
    • Released in pulses in a diurnal rhythmn
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Binds to adrenal cortex cells
    • Acts by increasing intracellular cAMP with G-protein
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Cushing’s disease -> Excess ACTH from corticotrophinoma pituitary tumours, leading to excess glucocorticoid secretion
    • Addison’s disease -> Deficiency of ACTH causes glucocorticoid deficiency
127
Q

Draw the hypothalamus-pituitary-adrenal axis.

A
128
Q

By what cells are FSH and LH secreted?

A

Gondaotroph cells (in the anterior pituitary)

129
Q

Describe the chemical nature of FSH and LH.

A

Glycoprotein hormone

130
Q

Describe the actions of LH and FSH in females and males.

A

Female (acts on the ovaries):

  • FSH stimulates follicle development and production
  • LH stimulates progesterone production

Male (acts on the testis):

  • FSH initiates and maintains spermatogenesis
  • LH stimulates testosterone production
131
Q

What are the receptors for FSH and LH?

A

G protein coupled to cAMP, on ovary/testes cells.

132
Q

Describe the control of FSH and LH release. What are they released in response to?

A
  • Stimulated by gonadotrophin-releasing hormone (GnRH) during reproductive life.
  • In females:
    • Inhibited by sex steroid oestrogen (negative feedback)
    • BUT switch to positive feedback triggers LH surge at ovulation.
    • Ovarian peptides (e.g. inhibin) inhibit FSH
  • In males:
    • LH release is inhibited by negative feedback from testosterone
133
Q

Describe when FSH and LH are released.

A
  • Hourly pulses of gonadotrophin releasing hormone (GnRH) during reproductive life maintain FSH and LH
  • However, there are cyclical variations in LH and FSH in the menstrual cycle due to feedback from the gonads
134
Q

Describe some dysfunctions of FSH and LH.

A
  • Infertility -> Deficiencies of LH and FSH or receptor dysfunction.
  • Precocious puberty -> Excess LH and FSH secretion (nearly always due to inappropriate hypothalamic GnRH secretion) or receptor overactivity.
135
Q

Draw the hypothalamus-pituitary-gonadal axis.

A
136
Q

For FSH and LH, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Glycoprotein
  • Site and mechanism of production & release
    • Released from pituitary gland
  • Stimuli that cause or inhibit its release
    • Feedback inhibition by gonadal hormones
  • Pattern of secretion into the blood/extracellular fluid
    • Released cyclically in menstrual cycle
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Binds to gonadal cells
    • Acts by increasing intracellular cAMP with G-protein
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Infertility -> Deficiencies of LH and FSH or receptor dysfunction.
    • Precocious puberty -> Excess LH and FSH secretion (nearly always due to inappropriate hypothalamic GnRH secretion) or receptor overactivity.
137
Q

By what cells is PRL secreted?

A

Lactotroph cells (in the anterior pituitary)

138
Q

Describe the chemical nature of PRL.

A

Protein hormone

139
Q

Describe the actions of PRL.

A
  • Stimulates the development and growth of breast and milk production
  • Inhibits the reproductive system at the level of the gonads and pituitary -> Lactational amenorrhea
140
Q

What is lactational amenorrhoea?

A
  • Natural postpartum infertility that occurs when a woman is not menstruating while breastfeeding.
  • This is due to PRL negative feedback on the HPG axis.
141
Q

What are the receptors for PRL?

A

Tyrosine kinase on breast cells.

142
Q

Describe the control of PRL release. What is it released in response to?

A
  • Stimulated by suckling and by oestrogen.
  • Inhibited by hypothalamus (via dopamine) -> Only pituitary hormone which is like this.
143
Q

Describe when PRL is released.

A

Released upon suckling.

144
Q

Describe some dysfunctions of PRL.

A

Hypersecretion of PRL can occur from PRL-secreting tumours in the pituitary gland termed ‘prolactinomas’ -> Causes galactorrhoea, infertility and impotence.

145
Q

Draw the hypothalamus-pituitary-breast axis.

A
146
Q

For PRL, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Protein
  • Site and mechanism of production & release
    • Released from pituitary gland
  • Stimuli that cause or inhibit its release
    • Stimulated by suckling and oestrogen
    • Inhibited by hypothalamus
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon suckling
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Binds to breast cells
    • Acts via a tyrosine kinase receptor
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • PRL-secreting tumours in the pituitary gland termed ‘prolactinomas’ causes galactorrhoea, infertility and impotence.
147
Q

By what cells is GH secreted?

A

Somatotroph cells (in the anterior pituitary)

148
Q

Describe the chemical nature of GH.

A

Protein hormone

149
Q

Describe the actions of GH.

A
  • Stimulates long bone and soft tissue growth -> Directly and indirectly by stimulating the release of IGFs (insulin-like growth factors) from the liver
  • Metabolic effects:
    • Insulin-like effects -> Promote amino acid uptake and promotes protein synthesis.
    • However, if GH is chronically increased it has anti-insulin effects. It is one of the hormones that switches metabolism away from glucose use and toward increased oxidation of fat (e.g. in starvation).
150
Q

What are the receptors for GH?

A

Tyrosine kinase on on various tissues.

151
Q

Describe the control of GH release. What is it released in response to?

A
  • Stimulated by hypoglycaemia, stress and exercise -> Due to growth hormone releasing hormone (GHRH) from the hypothalamus
  • Inhibited by somatostatin from the hypothalamus.
  • Inhibited by GH at the hypothalamus (negative feedback)
152
Q

Describe when GH is released.

A

Secreted in pulses every 4h, and on entering deep sleep.

153
Q

Describe some dysfunctions of GH.

A
  • Dwarfism -> GH insufficiency
  • Gigantism (in children) and acromegaly (in adults) -> GH excess
154
Q

For GH, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Protein
  • Site and mechanism of production & release
    • Released from pituitary gland
  • Stimuli that cause or inhibit its release
    • Stimulated by hypoglycaemia, stress and exercise -> Due to growth hormone releasing hormone (GHRH) from the hypothalamus
    • Inhibited by somatostatin from the hypothalamus
    • Inhibited by GH at the hypothalamus (negative feedback)
  • Pattern of secretion into the blood/extracellular fluid
    • Pulsatile release every 4 hours and upon entering deep sleep
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Binds to various cell types
    • Acts via a tyrosine kinase receptor
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Dwarfism
    • Gigantism/Acromegaly
155
Q

Draw the hypothalamus-pituitary-liver/muscle axis (for growth hormone).

A
156
Q

What is acromegaly?

A
157
Q

Describe the histological structure of the posterior pituitary.

A
  • There are the axons and terminals of magnocellular neurosecretory neurons originating in the hypothalamus.
  • Pituicytes (a type of glial supporting cell) surround and support the terminals.
158
Q

Describe how the hormones of the posterior pituitary are released.

A

The posterior pituitary hormones are synthesized in the hypothalamus, packed into granules, transported down the axons and released by exocytosis into the systemic veins draining the neurohypophysis.

159
Q

What controls the release of hormones from the posterior pituitary?

A

Entirely controlled by the hypothalamus.

160
Q

Whatm are the main hormones of the posterior pituitary?

A
  • Antidiuretic hormone (ADH) (a.k.a vasopressin)
  • Oxytocin
161
Q

Describe the chemical nature of ADH.

A

Peptide hormone

162
Q

Describe the actions of ADH.

A
  • Increases water reabsorption by acting in collecting ducts of kidney (V2)
  • Constricts peripheral arterioles and veins (V1)
163
Q

What are the receptors for ADH?

A
  • V2 receptors in kidney -> G protein coupled to cAMP
  • V1 receptors in vasculature -> PLC coupled
164
Q

Describe the control of ADH release. What is it released in response to?

A

Stimulated by increases in plasma osmolarity -> Sensitive to 1% increase from normal plasma OP - 285mOsm. This is sensed by hypothalamic osmoreceptors. These are also sensitive to decreases in blood volume or pressure.

165
Q

Describe some dysfunctions of ADH.

A

Diabetes insipidus

166
Q

What are the two types of diabetes insipidus?

A
  • Hypothalamic: Lack of ADH production
  • Nephrogenic: Lack of ADH action
167
Q

For ADH, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • Released from pituitary gland
  • Stimuli that cause or inhibit its release
    • Stimulated by increases in plasma osmolarity
    • Stimulated by decreases in blood volume or pressure
  • Pattern of secretion into the blood/extracellular fluid
    • CHECK
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • V2 receptors in kidney -> G protein coupled to cAMP
    • V1 receptors in vasculature -> PLC coupled
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Diabetes insipidus
168
Q

What are the two types of diabetes insipidus?

A
  • Hypothalamic: Lack of ADH production
  • Nephrogenic: Lack of ADH action
169
Q

Describe the chemical nature of oxytocin.

A

Peptide hormone

170
Q

Describe the actions of oxytocin.

A
  • Causes contraction of uterine myometrium in childbirth.
  • Causes ejection of milk.
  • Roles in social behaviour.
171
Q

What are the receptors for oxytocin?

A

G protein coupled receptors coupled to PLC in breast and uterine muscle.

172
Q

Describe the control of oxytocin release. What is it released in response to?

A
  • Stimulated by stretch of cervix/vagina during parturition -> Ferguson reflex
  • Stimulated by suckling -> Stimulation of the nipple causes the milk ejection reflex.
173
Q

Describe some dysfunctions of oxytocin.

A

Deficit of oxytocin may cause prolonged labour.

174
Q

For oxytocin, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • Released from pituitary gland
  • Stimuli that cause or inhibit its release
    • Stimulated by stretch of cervix/vagina during parturition -> Ferguson reflex
    • Stimulated by suckling -> Stimulation of the nipple causes the milk ejection reflex.
  • Pattern of secretion into the blood/extracellular fluid
    • CHECK
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • G protein couple to PLC in breast and uterus
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Deficit can produce prolonged labour
175
Q

Describe the effects of defects of different pituitary gland receptors.

A
  • ADH -> Failure leads to nephrogenic diabetes insipidus
  • GH -> Failure leads to abnormal short stature
  • ACTH -> Not known, receptor failure probably lethal because of role of cortisol in perinatal period
  • TSH -> Failure leads to rare form of cretinism
  • LH -> Failure leads to infertility, constitutive activity leads to precocious puberty.
176
Q

Describe the position and gross structure of the thyroid gland.

A
  • Isthmus (central part) lies anterior to 2nd to 4th tracheal rings.
  • The lateral lobes wrap around the trachea.
177
Q

How is the thyroid held in place?

A

Enclosed in fascia which anchors thyroid to the trachea.

178
Q

Describe the development of the thyroid gland.

A
  • A thyroid diverticulum forms in the midline of the floor of the mouth between the 1st & 3rd branchial arch components of the developing tongue.
  • It grows caudally over the developing larynx to the anterior aspect of the trachea.
  • As it descends it associates with the superior/inferior parathyroids which develop from the 4th/3rd pharyngeal pouches, and with neural crest cells which will form the parafollicular C (calcitonin) cells.
  • Two lateral lobes and a central isthmus form.
179
Q

Describe the blood supply to the thyroid.

A
  • Superior thyroid artery -> First branch of the external carotid artery.
  • Inferior thyroid artery -> Arises from the thyrocervical trunk (which in turn is a branch of the subclavian artery).
180
Q

What is a unique feature of the thyroid gland?

A

Its requirement for iodine.

181
Q

What is the only source of iodine to the body?

A

Dietary sources (fish, veg, etc.)

182
Q

What does the thyroid gland need iodine for?

A

Production of T3 and T4, which contain iodine.

183
Q

How does the thyroid store iodine?

A

Within the hormone precursor ‘thyroglobulin’ extracellularly.

184
Q

Describe the histological structure of the thyroid.

A
  • Follicular cells (epithelial) form follicles the lumen
  • The follicles are filled with ‘colloid’
  • Outside of the follicles there are parafollicular cells
185
Q

Label this structure of the thyroid.

A
186
Q

What is colloid?

A
  • The fluid that fills thyroid follicles
  • It contains thryoglobulin (the precursor to T4)
187
Q

What do follicular and parafollicular cells in the thyroid produce?

A
  • Follicular -> T4 (and some T3)
  • Parafollicular -> Calcitonin
188
Q

What produces thyroglobulin?

A

Follicular cells synthesise the thyroglobulin and secrete it into the colloid within the follicle.

189
Q

Compare the histological appearance of an active and inactive thyroid gland.

A
  • Active thyroid -> Follicular cells are tall and the colloid reduced in size
  • Inactive thyroid -> Follicular cells are low cuboidal and the follicles are filled with colloid.
190
Q

What is another name for parafollicular cells in the thyroid?

A

C cells

191
Q

What do parafollicular cells in the thyroid produce? What is its effet?

A
  • Calcitonin (a peptide hormone)
  • Acts to lower raised plasma calcium.
192
Q

How is iodine taken up into the thyroid from the plasma?

A

Sodium/iodide symporter on the basal membrane of follicular cells

193
Q

Which is the apical side of follicular cells?

A

The side that faces the colloid.

194
Q

Does the thyroid produce both T3 and T4?

A

It produces mostly T4, which is then metabolised to T3 peripherally.

195
Q

Describe how T4 (and T3) are produced in the thyroid.

A
  • Sodium/iodide symporter on the basal membrane of follicular cells pumps in iodide from the plasma
  • Thyroperoxidase enzyme on the apical plasmalemma:
    • Oxidises the iodide to iodine
    • Iodinates tyrosyl residues in the thyroglobulin anc couples tyrosyl residues
    • This produces the hormones T3 and T4 still bound in the thyroglobulin, hence inactive
  • Colloid is a store of thyroglobulin
  • Upon stimulation by TSH, the colloid is endocytosed and digested by lysosomes -> Frees T3 and T4.
196
Q

What are the full names for T3 and T4?

A
  • T3 = Tri-iodothyronine
  • T4 = Thyroxine
197
Q

What stimulates the production of T4 (and T3)?

A

TSH (Thyroid-stimulating hormone)

198
Q

Describe the control of T3/T4 production in the thyroid.

A
  • Stimulated by TSH from the anterior pituitary
    • TRH (thyrotrophin releasing hormone) controls TSH secretion from the anterior pituitary.
    • TRH is released in hyperglycaemia and cold
  • Inhibited by T3 and T4 (negative feedback on TSH production)
  • Iodide is also required
199
Q

Draw the hypothalamo-pituitary-thyroid axis.

A
200
Q

By what mechanism does TSH act in the pituitary gland?

A

Acts via cAMP.

201
Q

Name some plasma binding proteins that bind to thyroid hormones (T3 and T4). Describe their affinities for each.

[EXTRA]

A
  • Thyronine-binding globulin (TBG) -> Glycoprotein with higher affinity for T4 than T3, produced by the liver.
  • Transthyretin -> Lower affinity for T4, T3.
  • Albumin -> Very low affinity, but high capacity.
202
Q

Where is the inactive T4 converted into the active T3?

A

In the liver and kidney, mostly.

203
Q

What type of enzyme is involved in the metabolism of T4?

A

Deiodinases

204
Q

What are the different enzymes that act on T4?

A
  • Type I deiodinase converts T4 to active T3 in the liver
  • Type II deiodinase converts T4 to active T3 in the pituitary
  • Type III deiodinase converts T4 to the inactive T3r in the liver
205
Q

What determines whether T4 is deiodinated to the active T3 or inactive rT3?

A

Controlled by the need for metabolism:

  • Rreduced in starvation due to raised cortisol
  • Reduced in severe illness
  • Reduced by propranolol
206
Q

How are iodothyronines (e.g. T4 and T3) ultimately degraded?

A
  • Iodothyronines are finally deiodinated to thyronine
  • Iodide is salvaged by the kidney and reused.
207
Q

Describe the mechanism of action of T3.

A
  • T3 is transported into cells and acts on nuclear receptors (TR) which act on response elements (TREs) in gene promoters
  • This interaction results in stimulation or inhibition of the production of many different mRNAs and therefore proteins
208
Q

On what tissues does T3 act?

A

T3 acts on almost every tissue of the body but has little metabolic effect in the brain, spleen or testis. It also has developmental effects on some tissues.

209
Q

What are the actions of T3? [IMPORTANT]

A
  • Increases basal metabolic rate:
    • Increases production of Na+/K+ ATPase (which uses 20-45% of all ATP)
    • Proteins -> Increases protein degradation
    • Carbohydrates -> Increases glycogenolysis and gluconeogenesis. Potentiates insulin effects increasing glycogenesis and glucose usage.
    • Lipids -> Stimulates cholesterol breakdown and enhances lipolysis
    • Stimulates production of ß adrenergic receptors and TRH receptors
  • Developmental effects:
    • CNS -> Essential for postnatal growth of CNS; stimulates production of myelin, neurotransmitters and axonal growth
    • Bone -> Stimulates linear growth by effects on chondrocytes
    • Stimulates normal development, maturation and eruption of teeth, hair and epidermis
  • Cardiovascular effects -> Increases cardiac output, rate and force
  • Stimulates gut motility
  • Stimulates bone turnover
  • Increases muscle contraction
210
Q

How does T3 have cardiovascular effects?

A
  • Increases production of myosin, beta-1 receptors and Ca2+-ATPase
  • These proteins increase contractility
211
Q

Is T3 anabolic or catabolic?

A

At low doses, it is more anabolic. At high doses, it is more catabolic.

212
Q

How do T3 and T4 provide negative feedback?

A

They act on the pituitary and hypothalamus, affecting the hypothalamo-pituitary-thyroid axis.

213
Q

What is enlargement of the thyroid called?

A

Goitre

214
Q

What can be some causes of goitre (enlargement of the thyroid)?

A
  • Iodine deficiency -> Lack of T3/T4 means there is no feedback on TRH and TSH secretion (TSH stimulates thyroid growth)
  • Graves’ disease -> Overactivation of the TSH receptor
  • Tumour -> May be functioning or not.
215
Q

What are the causes, indicators and symptoms of hyperthyroidism?

A

Causes:

  • Graves’ disease -> Generally due to autoimmune production of immunoglobulins that mimic TSH
  • Tumours of thyroid follicular cells

Indicators:

  • High T3 and T4
  • Low TSH

Symptoms:

  • Raised BMR
  • Fast, bounding pulse
  • Heat intolerance
  • Weight loss despite a large appetite
  • Increased sympathetic drive
  • Eye protrusion
216
Q

What is another name for hyperthyroidism? [IMPORTANT]

A

Thyrotoxicosis

217
Q

What are the causes, indicators and symptoms of hypothyroidism?

A

Causes:

  • Failure of production by thyroid
  • Lack of iodine
  • Autoimmune inhibition
  • Failure of thyroid development
  • Failure of pituitary to produce TSH or hypothalamus TRH (‘central’ hypothyroidism)
  • Thyroid hormone resistance -> Inactivating mutation of thyroid hormone receptor
  • Failure of thyroid hormone transporters

Indicators:

  • Low T3 and T4
  • High TSH

Symptoms:

  • Reduced metabolism
  • Slow mentation
  • Hypothermia
  • Constipation
218
Q

What are the prenatal and adult forms of hypothyroidism called? What are the symptoms of each? [IMPORTANT]

A
  • Cretinism (prenatal) -> Gross deficits in CNS myelination and stunting of postnatal growth if untreated (this is due to the importance of T3 in development)
  • Myxoedema (adult) -> Reduced metabolism, slow mentation, hypothermia, constipation.
219
Q

What is thyroid hormone resistance and how does it present?

A
  • A number of genetic defects in the thyroid receptor reduce hormone binding.
  • The subject is hypothyroid but will have normal levels of plasma hormone.
220
Q

How can hypothyroidism be treated?

A

Administering thyroxine (T4).

221
Q

How can Graves disease be treated?

A
  • It is caused by autoimmune antibodies that bind and activate TSH receptors.
  • TSH R stimulates enlargement of thyroid gland.
  • So you can treat it with radioactive iodine I-131.
222
Q

What are some different drugs that alter thyroid activity?

A
  • Thyroxine is given for hypothyroidism
  • Iodine: In large doses reduces the activity/vascularity of the gland
  • Radioactive iodine I-131 can be given to destroy thyroid tissue by local irradiation.
223
Q

For T3, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • CHECK
  • Site and mechanism of production & release
    • Released from thyroid gland by exocytosis as T4
    • T4 is converted to T3 in the liver by deiodinase I enzyme
  • Stimuli that cause or inhibit its release
    • Stimulated by TSH from the pituitary
      • Stimulated by hyperglycaemia stimulates
      • Inhibited by hypoglycaemia inhibits
      • Stimulated by cold stimulates
  • Pattern of secretion into the blood/extracellular fluid
    • CHECK
  • Mechanism of transport in the blood/extracellular fluid
    • Bound to thyronine-binding globulin (TBG), transthyretin and albumin
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Acts on many different tissues
    • Binds to nuclear receptors, which affect transcription
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Excess -> Thyrotoxicosis
    • Deficiency -> Cretinism, Myxoedema
    • Goitre
    • Thyroid hormone resistance
224
Q

What is PTH?

A

Parathyroid hormone

225
Q

What is the chemical class of PTH?

A

Peptide hormone

226
Q

Describe when PTH is released and what its action is.

A
  • Released in response to low plasma calcium
  • PTH restores low plasma Ca2+ to normal
227
Q

What is stress?

A

A change that threatens to disturb homeostasis:

  • Physical
    • Trauma
    • Infection
    • Intense heat or cold
    • Starvation
    • Surgery
    • Severe blood loss
    • Pain
    • Dehydration
  • Psychological
    • Anxiety
    • Depression
228
Q

What are the inner and outer parts of the adrenal glands called?

A
  • Inner -> Medulla
  • Outer -> Cortex
229
Q

Describe the histology and function of the adrenal glands.

A
  • Inner medulla
    • Made up of groups of chromaffin cells packed with catecholamine granules -> Store large amounts of adrenaline and noradrenaline.
  • Outer cortex
    • Made up of sheets of cells surrounded by capillaries and arranged in three zones:
      • Outer zona glomerulosa -> Makes aldosterone
      • Middle zona fasciculata -> Makes cortisol
      • Inner zona reticularis -> Makes androgens
230
Q

Label this histological diagram of the adrenal gland. Include the hormones released by each layer.

A

Medulla produces catecholamines.

231
Q

Describe the position of the adrenal glands.

A

Just medial to the upper pole of each kidney.

232
Q

Describe the development of the adrenal glands. [IMPORTANT]

A
  • Medulla develops from neural crest
  • Cortex develops from mesoderm close to the mesonephros.
  • Early adrenal gland is composed of a fetal zone and a definitive zone
  • ‘Fetal zone’ of the adrenal cortex is very prominent in the fetus but it regresses after birth. The definitive zone is similar to the adult adrenal cortex.
233
Q

What is the importance of the fetal zone of the adrenal cortex?

A

The fetal zone produces androgens which the placenta aromatizes to oestrogens. It regresses after birth.

234
Q

Describe the blood supply and drainage of the adrenal glands. [IMPORTANT]

A

Arterial supply:

  • Branches of the inferior phrenic artery, the renal arteries and the aorta.
  • These small arteries form an arterial plexus beneath the capsule surrounding the adrenal and then enter a sinusoidal system that penetrates the cortex and the medulla draining into a single central adrenal vein in each gland.

Venous drainage:

  • The veins drain to the inferior vena cava (R) and renal vein (L).
235
Q

Describe the innervation of the adrenal glands.

A
  • Principally to the medulla.
  • Innervated by thoracic preganglionic sympathetic nerves which release ACh, acts at nicotinic receptors -> NOTE that this is unusual because there are no post-ganglionic nerves.
236
Q

What is the role of the adrenal medulla?

A

Enabling the fight or flight response via release of catecholamines into the bloodstream.

237
Q

Draw a diagram to show how the adrenal medulla is stimulated.

A
238
Q

Describe the sythesis of adrenaline in the adrenal medulla.

A
  • In the cytoplasm of chromaffin cells, tyrosine is converted to DOPA by tyrosine hydroxylase
  • DOPA is converted to dopamine by DOPA decarboxylase
  • Dopamine is then pumped into granules and is converted to noradrenaline by dopamine beta hydroxylase
  • Noradrenaline is then stored or pumped out of the granule for conversion to adrenaline (80% of total) by phenyl-N-methyl transferase (PNMT) in the cytoplasm.
  • Adrenaline is then pumped into granules for storage and release.
239
Q

Is the adrenal medulla necessary for the emergency response to stress?

A

The adrenal medulla contributes 10% of the total sympathetic nervous system response to stress so thus it is not vital.

240
Q

Summarise the effects of catecholamines on the body.

A
241
Q

What is the general function of the adrenal cortex?

A

The maintenance of essential processes in chronic stress.

242
Q

What type of hormones does the adrenal cortex secrete?

A

(Cortico)Steroid hormones

243
Q

What are the main hormones produced by the adrenal cortex?

A
  • Glucocorticoids (cortisol)
  • Aldosterone
  • Androgens
244
Q

What do the different zones of the adrenal cortex release?

A

From outside to inside:

  • Zona glomerulosa -> Aldosterone
  • Zona fasciculata -> Cortisol
  • Zona reticularis -> Androgens
245
Q

What are corticosteroids and what are the different types?

A
  • Corticosteroids are hormones produced by the adrenal cortex
  • The two main types:
    • Mineralcorticoids
      • Produced in the zona glomerulosa
      • e.g. Aldosterone
    • Glucocorticoids
      • Produced in the zona fasciculata
      • e.g. Cortisol
246
Q

How are the steroid hormones in the adrenal cortex synthesised?

A

Glucocorticoids and mineralcorticoids are synthesised from cholesterol (details are not needed).

247
Q

Describe how each of the adrenal cortex steroids is transported in the blood.

A
  • All adrenal steroids are bound by albumin
  • Cortisol -> Bound by cortisol-binding globulin
  • Aldosterone -> No high affinity binding protein
  • Androgens -> Sex steroid binding globulins
248
Q

How are adrenal cortex steroids cleared from the blood?

A
  • The kidney filters free steroid hormone but reabsorbs 90%.
  • The liver converts steroid hormones to hydrophilic metabolites by hydroxylation and conjugation reactions.
249
Q

Draw the hypothalamus-pituitary-adrenal axis.

A
250
Q

How do adrenal cortex steroid hormones act?

A

They act on intracellular receptors that control gene transcription.

251
Q

What adrenal hormone is involved in the hypothalamus-pituitary-adrenal axis?

A

Cortisol

252
Q

What are glucocorticoids and what is the main one?

A
  • Adrenal hormones that preserve glucose for the brain
  • The main one is cortisol
253
Q

What are the actions of cortisol (a glucocorticoid)?

A
  • Accelerate gluconeogenesis in liver
  • Accelerate lipolysis and protein catabolism in liver and peripheral tissues
  • Central nervous system activity (appetite, mood)
  • Increased red blood cell production
  • Maintenance of circulation
  • Reduce inflammation and the immune response
254
Q

Describe the metabolism of cortisol.

A

Cortisol is converted in the liver to the relatively inactive metabolite, cortisone, by 11 ß-hydroxysteroid dehydrogenase.

255
Q

Describe the control of cortisol (a glucocorticoid) output.

A
  • Hypothalamus releases corticotrophin releasing factor (CRF) in response to stress (inhibited by cortisol negative feedback).
  • CRF acts on anterior pituitary corticotrophs to stimulate ACTH production and release
  • ACTH stimulates the zona fasciculata cells via cyclic AMP to stimulate cortisol production.
256
Q

What are some clinical uses of glucocorticoids?

A
  • Inflammatory disorders, arthritis, asthma
  • Inhibit transplant rejection
  • Chemotherapy
  • Antenatal to mature the lungs in fetus threatening preterm labour
257
Q

What are some deficiencies of cortisol (glucocorticoid) action?

A
  • Insufficiency -> Addison’s
  • Excess -> Cushing’s
258
Q

Draw the cause and symptoms of Cushing’s disease.

A

Cause: Excess cortisol (glucocorticoids)

259
Q

Draw the causes and symptoms of Addison’s disease.

A
260
Q

How can the effects of cortisol on the immune system be exploited clinically?

A

Glucocorticoids have immunosuppressant effects.

261
Q

What type of hormone is aldosterone?

A

Mineralcorticoid

262
Q

What are the actions of aldosterone?

A
  • In kidney collecting tubules:
    • Stimulates reabsorption of Na+ in exchange for secretion of K+ , H+ , NH3 +
  • In salivary and sweat glands:
    • Regulates ion transport to retain sodium.
263
Q

Describe the receptors (and their location) for mineralcorticoids.

A
  • Mineralocorticoid receptors are present in the nuclei of only a few cell types -> Kidney collecting tubule epithelia, salivary and sweat glands.
  • However, cortisol also binds to MR. Therefore, in aldosterone targets cortisol is deactivated to protect MR from cortisol activation.
264
Q

Describe the control of aldosterone secretion.

A

Renin-angiotensin system:

  • RAA axis is stimulated by low plasma Na+ or low renal blood pressure.
  • This stimulates renin release which acts in the lung to stimulate conversion of angiotensin I to Angiotensin II (AII) by activating angiotensin converting enzyme (ACE).
  • Angiotensin II stimulates output of aldosterone from the zona glomerulosa of the adrenal cortex (it also causes arteriolar constriction and drinking in response to thirst).
265
Q

What are some deficiencies of aldosterone?

A
  • Hypoaldosteronism (in adrenal failure)
    • Results in sodium loss, low blood volume and low blood pressure.
  • Hyperaldosteronism (Conn’s syndrome)
    • Results in excess sodium retention, water retention and increased blood pressure.
266
Q

Give an example of a drug that influences aldosterone action.

A

Spironolactone is an aldosterone antagonist used as an anti-hypertensive.

267
Q

Are adrenal androgens a large part of adrenal secretions?

A

No, at most times they are a very minor component of secretion.

268
Q

What is the main adrenal androgen?

A

DHEA = Dehydroepiandrosterone

269
Q

What is the function fo DHEA?

A

It is a weak androgen which stimulates axillary/pubic hair development at puberty, and libido.

270
Q

Describe how release of DHEA is controlled.

A

It is stimulated by ACTH.

271
Q

Add flashcards on the individual hormones.

A
272
Q

For adrenaline, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Amine
  • Site and mechanism of production & release
    • Formed by a sequence of reactions
    • Stored in granules in chromaffin cells of the adrenal medulla
    • Released by exocytosis
  • Stimuli that cause or inhibit its release
    • Stimulated by sympathetic stimulation of the adrenal medulla
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Binds to alpha and beta adrenoceptors
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Adrenal medulla is removed the adrenal medulla stress response is compensated for by the remainder of the sympathetic system.
    • Tumours of the adrenal medulla (phaeochromocytoma) constantly secrete catecholamines causing hypertension, tremor, anxiety, forceful heartbeat.
273
Q

For DHEA, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Steroid
  • Site and mechanism of production & release
    • Produced in zona reticularis
    • Synthesised from cholesterol
  • Stimuli that cause or inhibit its release
    • Stimulated by ACTH from the hypothalamus
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • Binds to sex steroid binding globulin
    • Binds to albumin with low affinity
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Acts on nuclear receptors to affect transcription
    • Stimulates axillary/pubic hair development at puberty, and libido.
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • CHECK
274
Q

For aldosterone, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Steroid
  • Site and mechanism of production & release
    • Produced in zona glomerulosa
    • Synthesised from cholesterol
  • Stimuli that cause or inhibit its release
    • Stimulated by RAA axis in response to decreased blood pressure
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • No high affinity binding proteins
    • Binds to albumin with low affinity
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Acts on nuclear receptors to affect transcription
    • In kidney collecting tubules -> Increases sodium retention in exchange for potassium
    • In salivary and sweat glands -> Increases sodium retention
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Hypoaldosteronism (in adrenal failure) -> Results in sodium loss, low blood volume and low blood pressure.
    • Hyperaldosteronism (Conn’s syndrome) -> Results in excess sodium retention, water retention and increased blood pressure.
275
Q

For cortisol, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Steroid
  • Site and mechanism of production & release
    • Produced in zona fasciculata
    • Synthesised from cholesterol
  • Stimuli that cause or inhibit its release
    • Stimulated by ACTH (which in turn is stimulated by corticotrophin releasing factor, CRF, from the hypothalamus, which is released in response to stress
    • Inhibited by cortisol negative feedback on the hypothalamus
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • Binds to cortisol-binding protein
    • Binds to albumin with low affinity
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Widespread effects in different tissues
    • Acts on nuclear receptors to affect transcription
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Cortisol insufficiency -> Addison’s disease
    • Cortisol excess -> Cushing’s syndrome
276
Q

Name the different GI hormones and where they are produced in the GI tract.

A

The ones highlighted are those mentioned in the spec, along with secretin.

277
Q

What are the 4 major classifications of GI hormones?

A
  • Hormones which regulate digestion
  • Hormones which regulate digestion and appetite
  • Hormones which regulate appetite and feeding
  • Incretins (hormones which regulate insulin secretion)
278
Q

State the main GI hormones that fall under these categories:

  • Hormones which regulate digestion
  • Hormones which regulate digestion and appetite
  • Hormones which regulate appetite and feeding
  • Incretins (hormones which regulate insulin secretion)
A
279
Q

What are GI hormones released in response to?

A

Endocrine cells scattered in the gut epithelium sense the contents of the lumen. Smell and taste also contribute.

280
Q

Describe the polarity of gut endocrine cells.

A
  • Hormone secreted basally
  • Most have microvilli on apex open to gut lumen to sense the content of the gut
281
Q

What is the chemical class of GI hormones? [IMPORTANT]

A

Peptides

282
Q

How are GI hormones inactivated?

A

Cleavage by peptidases (since they are peptide hormones)

283
Q

How do endocrine cells in the GI tract respond to the presence of food in the GI tract?

A

Enteroendocrine cells are electrically active and fire action potentials in response to the presence of digested food in the GI tract.

284
Q

What is the action of histamine?

A

Stimulates gastric acid (HCl) secretion from the stomach.

285
Q

What cells in histamine secreted by?

A

Enterochromaffin-like (ECL) cells of the stomach

286
Q

What is histamine secreted in response to?

A

Stretch or vagal stimulation of the stomach

287
Q

On what receptors (and cells) does histamine act?

A

H2 receptors on the oxyntic cells of the stomach

288
Q

For histamine, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • Produced from histidine by histidine decarboxylase
    • Produced in ECL (enterochromaffin-like) cells of the stomach
    • Secreted by exocytosis
  • Stimuli that cause or inhibit its release
    • Stimulated by stretch or vagal stimulation of the stomach
    • Stimulated by gastrin (which also has an acid secreting effect of its own)
    • Inhibited by somatostatin
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Stimulates HCl secretion from oxyntic cells of the stomach
    • Acts on H2 receptors
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • CHECK
289
Q

Where cells is gastrin secreted by?

A

G cells of the gastric antrum

290
Q

What are the stimuli and inhbitors of gastrin release?

A

Stimulated by:

  • Protein digestion products
  • Vagus stimulation
  • Stretch of stomach
  • Hypercalcaemia

Inhibited by:

  • H+ (negative feedback)
  • Somatostatin (local negative feedback)
291
Q

What are the actions of gastrin?

A
  • Gastric acid secretion (direct & indirect via stimulating histamine H2 )
    • Induces the insertion of K+/H+-ATPase pumps into the apical membrane of parietal cells
  • Pepsinogen secretion

Others (not in spec):

  • Parietal cell growth
  • Antral motility (churning)
  • Mucosal blood flow
  • Trophic to parts of GI tract
  • Water & electrolyte secretion in liver, pancreas, intestine.
292
Q

Draw a diagram to show how gastrin, histamine and somatostatin act to regulate HCl secretion in the stomach.

A
  • The parasympathetic (vagal) stimulation of histamine-releasing ECL cells causes release of histamine
  • Parasympathetic stimulation of gastrin-releasing G cells causes release of gastrin, which also promotes further histamine release
  • Histamine and gastrin together cause insertion of the H+/K+-ATPase into the apical membrane of the endocrine cells in the stomach lining -> This acidifies the stomach
  • These actions are inhibited by somatostatin from D cells
293
Q

For gastrin, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • G cells of the gastric antrum
    • Produced as preprogastrin and released by exocytosis
  • Stimuli that cause or inhibit its release
    • Stimulated by:
      • Protein digestion products
      • Vagus stimulation
      • Stretch of stomach
      • Hypercalcaemia
    • Inhibited by:
      • H+ (negative feedback)
      • Somatostatin (local negative feedback)
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Stimulates gastric acid secretion (direct & indirect via stimulating histamine H2)
      • Induces the insertion of K+/H+-ATPase pumps into the apical membrane of parietal cells
    • Stimulates pepsinogen secretion
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • CHECK
294
Q

What cells is secretin secreted by?

A
  • S cells, from duodenum to distal ileum
  • These are in the neck region of intestinal glands
295
Q

What are the stimuli and inhibitors of secretin release?

A
  • Stimulated by acid in proximal duodenal lumen
  • Inhibited by somatostatin
296
Q

What are the actions of secretin?

A
  • Stimulates secretion of HCO3- and water from the pancreas and liver
    • Washes pancreatic secretions into the duodenum
    • Washes bile too
297
Q

By what mechanism does secretin have its action?

A
  • It leads to secretion of HCO3- and water from the pancreas and liver
  • This is done by stimulation of Gs-coupled GPCRs that lead to increases in cAMP -> This acts on CFTR, leading to changes in Cl- conductance that drives Cl-/HCO3- exchange.
298
Q

For somatostatin, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • D cells from the gastric antrum to the colon
    • Released by exocytosis
  • Stimuli that cause or inhibit its release
    • Stimulated by meals: amino acids, glucose, fatty acids, gastrin, secretin
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Suppresses secretion of GI hormones
    • Suppresses their effects (acid etc)
    • Retards absorption of glucose; protects against post-prandial hyperglycaemia (in liver)
    • Acts via Gi GPCRs that lead to decreases in intracellular cAMP
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • Somatostatinoma
299
Q

For secretin, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • S cells of the duodenum to ileum
    • Released by exocytosis
  • Stimuli that cause or inhibit its release
    • Stimulated by:
      • Acid in the duodenum
    • Inhibited by:
      • Somatostatin
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • It leads to secretion of HCO3- and water from the pancreas and liver
    • This is done by stimulation of Gs-coupled GPCRs that lead to increases in cAMP -> This acts on CFTR, leading to changes in Cl- conductance that drives Cl-/HCO3- exchange.
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • CHECK
300
Q

What does CCK stand for?

A

Cholecystokinin (a.k.a. pancreozymin)

301
Q

What cells is CCK secreted by?

A

I cells in the duodenum and jejunum

302
Q

What are the actions of CCK?

A
  • Suppresses appetite
  • Stimulates pancreatic secretions
  • Stimulates gall bladder contraction
  • Inhbits stomach emptying and stimulates gut motility
  • Potentiates action of secretin (stomach acid secretion)
303
Q

How does CCK act on appetite?

A
  • CCK acts on vagal afferent terminals to signal satiety, acts on vagal terminals -> Inhibits feeding, therefore neurocrine rather than endocrine
  • Cholecystokinin 1 (CCK1) receptor on the vagus nerve
304
Q

What are the stimuli for CCK secretion?

A

Products of protein and fat digestion in the duodenum

305
Q

For CCK, summarise:

  • Chemical class & broad structure
  • Site and mechanism of production & release
  • Stimuli that cause or inhibit its release
  • Pattern of secretion into the blood/extracellular fluid
  • Mechanism of transport in the blood/extracellular fluid
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
A
  • Chemical class & broad structure
    • Peptide
  • Site and mechanism of production & release
    • S cells of the duodenum to ileum
    • Released by exocytosis
  • Stimuli that cause or inhibit its release
    • Stimulated by:
      • Acid in the duodenum
    • Inhibited by:
      • Somatostatin
  • Pattern of secretion into the blood/extracellular fluid
    • Released upon stimulation
  • Mechanism of transport in the blood/extracellular fluid
    • CHECK
  • Principal target tissue(s) & receptors -> Mechanism of action in target tissue(s)
    • Suppresses appetite
    • Stimulates pancreatic secretions
    • Stimulates gall bladder contraction
    • Inhbits stomach emptying and stimulates gut motility
    • Potentiates action of secretin (stomach acid secretion)
  • Principal effects of normal hormone levels, excess and deficiency and hormone resistance in target
    • CHECK
306
Q

What are incretins and what are the two main ones?

A
  • Hormones which regulate postprandial insulin release
  • Two main examples:
    • GLP -> Glucagon-like peptide
    • GIP -> Glucose-dependent insulinotropic peptide
307
Q

For GLP, summarise the release site, stimuli for release and actions.

A

GLP also has a system-wide positive metabolic effect, e.g. on the heart, etc.

308
Q

What produced erythropoietin?

A

Kidneys

309
Q

What are the main types of eicosanoids you need to know about?

A
  • Prostaglandins
  • Prostacyclin
  • Thromboxanes
310
Q

What are eicosanoids produced from?

A

Arachidonic acid

311
Q

What are the roles of prostaglandins?

A
  • Vasodilator
  • Prevent aggregation of platelets
  • Stimulate uterine contractions
312
Q

What is prostacyclin?

A

A prostaglandin that plays a role in vasodilation.

313
Q

What is an inhibitor of prostaglandin synthesis?

A

Aspirin

314
Q
A

YEAR 1 - Organisation of the Body (Anton) (15 decks)

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