Hormone Synthesis and Action Flashcards

1
Q

what are the 3 different types of glands?

A

Exocrine
Endocrine
mixed glands

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2
Q

what are endocrine glands?

A

ductless glands which secrete hormones, produced by cells, directly into the blood to be then carried to their target organs

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3
Q

what are exocrine glands?

A
  • release their secretions outside the body (not in blood, or plasma) and may be ducted e.g. salivary glands, sweat glands
  • not part of the endocrine system
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4
Q

what are mixed glands?

A

both exo and endocrine
e.g. Pancreas produces digestive juice which enter into the intestine (exo) but also produce insulin, glucagon and somatostatin which are secreted directly into the blood (endo)

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5
Q

what are the main glands in the body?

A

hypothalamus
pituitary gland
thyroid gland
adrenal glands
gonads- testes, ovaries

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6
Q

what are the two major regulatory systems in the body and what do they do?

A

endocrine
nervous
monitor and maintain internal and external environment (homeostasis)

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7
Q

what are the differences in nervous and endocrine system?

A

chemical component:
nervous- few neurotransmitters
endocrine- many hormones

speed of effect:
nervous- generally rapid
endocrine- generally slow

duration of effect:
nervous- short lived (neurotransmitter broken down very quickly)
endocrine- long lasting (takes time for hormones to be broken down)

localisation of effect:
nervous- localised (cell to cell)
endocrine- widespread (in blood)

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8
Q

what are the 6 different mechanisms of chemical signalling? (JAPINE)

A

endocrine
autocrine
intracrine
paracrine
juxtacrine
neuroendocrine

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9
Q

what is endocrine secretion?

A

secretes hormone directly into bloodstream which then acts on a distant target tissue.

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10
Q

what is autocrine secretion?

A

The hormone leaves the cell and then docks back onto the same cell via its receptors

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11
Q

what is intracrine secretion?

A

cell synthesise its own hormone which then acts within the cell (hormone does not leave the cell)

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12
Q

what is paracrine secretion?

A

secreted hormone acts on nearby cells within tissue or organ.

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13
Q

what is juxtacrine secretion?

A

secreted hormone acts on neighbouring cells

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14
Q

what is a neuroendocrine secretion?

A

An electrical stimulus passes down a neurone (e.g. in the Hypothalamus) to a specialised cell causing it to secrete a hormone which will affect a distant target cell.

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15
Q

what are the 2 ways in which hormone release is controlled?

A

positive and negative feedback

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16
Q

what is negative feedback?

A

most common
process by which body senses change and activates mechanism to reduce it

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17
Q

describe the process in which your body controls an action through negative feedback?

A

stimulus e.g. youre cold
hypothalamus recognises that
secretes a specific hormone to counteract change
hormone goes to target tissue e.g increasing metabolism
the SAME hormone usually (or another hormone) will negatively feedback and switch the system off

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18
Q

what is positive feedback?

A

process by which body senses change and activates mechanism to amplify it. Positive feedback is where hormone feedback is enhanced

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19
Q

define endocrine axis and give an example

A

How the glands are interact with each other.
e.g. Hypothalamus-pituitary-adrenal (HPA) axis

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20
Q

what is the hypothalamo-pituitary axis?

A

a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis

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21
Q

what are tropic hormones and what is their role?

A

hormones that have other endocrine glands as their target e.g. TRH, TSH, CRH and ACTH.

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22
Q

what happens in the Hypothalamic-pituitary-Adrenal axis?

A
  • The hypothalamus secrete CRH, which stimulates cells in the anterior pituitary to secrete ACTH.
  • ACTH binds to receptors on the adrenal cortex, stimulating release of cortisol hormones.
  • When blood concentrations of cortisol hormones increase above a certain threshold, cortisol inhibits the secretion of CRH from the hypothalamus and ACTH from the pituitary gland to stop the cortisol from being produced in excess.
  • This is an example of “negative feedback”.
23
Q

what happens in the Hypothalamic-pituitary-Thyroid axis?

A
  • Neurons in the hypothalamus secrete thyrotropin releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone (TSH).
  • TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body.
  • When blood concentrations of thyroid hormones increase above a certain threshold, both T4 and T3 inhibit secretion of TRH from the hypothalamus and TSH from the pituitary gland to stop the thyroid hormones from being produced in excess. - This is an example of “negative feedback”.
24
Q

what are the 3 main groups of hormones? (give examples)

A

Protein/peptide hormones (Example: Insulin)
Steroid hormones (Example: Cortisol)
Amine hormones (Example: Thyroxine)

25
Q

what are properties of peptide hormones?

A
  • made of chains of amino acids
  • Water soluble (hydrophilic) So are transported in the blood easily but they can’t get into a cell as can’t get past the lipid bilayer. So they must bind to receptors on the cell surface.
  • Stored in membrane bound vesicles ready for release by exocytosis. This means there is no delay once signal comes in. (Very rapid response)
  • For hormone therapy peptide hormones needs to be injected into the blood otherwise degraded in gastrointestinal tract.
26
Q

how are peptide hormones made?

A
  • Produced on ribosomes (RER) as large precursor molecule - pre-prohormone
    (Pre-prohormone → prohormone → hormone) which are inactive at first (when its a Pre-prohormone and prohormone) until its put in vesicle and taken to the Golgi where the final modifIcations are made and its activated
27
Q

how are hormones synthesised?

A

Transcription of gene –> pre-mRNA –> mRNA leaves the nucleus to RER for translation of protein from mRNA at a ribosome. This is the Preprohormone.
In the RER a signal sequence is cleaved off the Preprohormone to produce the prohormone.
The prohormone is then packaged into transport vesicles and enters the golgi
Golgi for post- translational changes e.g. glycosylation
Packaged in secretory vesicles which contain lysosomes which cleave off unnecessary sections to produce the active hormone.
Exocytosis

28
Q

explain how thyrotropin releasing hormones (TRH) are made?

A

TRH is synthesised from a large precursor protein which contains several copies.
Precursor is then cleaved (via proteolysis) to give active small peptide hormone (TRH)
Proteolysis: process of cutting the protein.

29
Q

what is proteolysis?

A

process of cutting the protein

30
Q

how is ACTH produced?

A

found in a long protein chain that has lots of different inactive proteins
In the corticotroph (cell in anterior pituitary), POMC (another protein) is cleaved to produces one ACTH

31
Q

what hormones are produced with alpha and beta subunits and how are they activated?

A

TSH, hCG, LH, FSH are initially produced with both alpha and beta subunit.
The alpha subunit is the SAME for all of them.
The beta is DIFFERENT (the active hormone).
So, in processing the beta-subunit is cleaved from alpha giving distinct active hormones.

32
Q

what are steroid hormones made from (in general)?

A

All made from cholesterol

33
Q

what are the properties of steroid hormones?

A

Steroid Hormones come from adrenal cortex or are sex hormones
Hydrophobic - so need a carrier protein when traveling in blood
They are lipid soluble so they can pass through the lipid bilayer.
Synthesised as required and then rapidly diffuse out of the cell.

34
Q

why can’t steroid hormones be stored?

A

lipid soluble- can’t be stored because once made they’ll just diffuse straight through lipid bilayer

35
Q

how are steroid hormones synthesised?

A
  • Esters are first hydrolysed to release cholesterol
  • Enzyme CYP11A first convers cholesterol into Pregnenolone (in the mitochondria) (this is the rate limiting step)
  • Pregnenolone then becomes the starting point for all the other steroids e.g. glucocorticoid, mineral corticoids and sex steroids (androgens and oestrogens)
  • Pregnanolone is then processed by enzymes in SER to produce the hormone.
36
Q

how are steroid hormones eliminated?

A

by inactivating metabolic transformations and also by excretion in urine or bile

37
Q

how are adrenal glands able to produce steroid hormones?

A

The cells in the different layers of the adrenal gland all have the specific enzymes are necessary for the production of the specific steroid hormone to be produced from pregnenolone.
they have 3 cortical regions that produce different products

38
Q

what are the 3 cortical regions in the adrenal glands that produce steroid hormones?

A

zona glomerulosa (its cells produce enzymes to convert pregnenolone to - aldosterone
zona fasciculata (etc.) - cortisol
zona reticularis (etc.) - adrenal androgens

39
Q

why aren’t adrenal androgens activated?

A
  • the adrenal androgens are precursors to sex steroids
  • they are inactive in the adrenal glands
  • they are activated in another region of the body
  • zona glomerulosa- the cells here do NOT express the enzymes necessary for cortisol synthesis or sex steroid synthesis
40
Q

what are amine hormones made out of?

A

tyrosine derivatives bound together.
synthesised in the thyroid gland

41
Q

what are amine hormones properties?

A

Small, hydrophobic - so need a transporter in the blood.
Lipid soluble - so they can pass through the lipid bilayer.

42
Q

what are T4 and T3 hormones?

A

T4 prohormone - Contain 4 iodine atoms
T3 Active hormone - Contain 3 iodine atoms

43
Q

explain the process in which thyroid hormones are produced? (13 steps)

A

1) Iodide ions (from the diet) enters the blood
2) It is then taken into follicular cells by sodium/I symporter (allows much higher conc. of iodide inside thyroid).
3) The iodine ions then leave cell into the colloid through the Pendrin protein on the apical surface.
Iodide ions then oxidized to I. This is catalysed by TPO.
4) Protein synthesis in the follicular cells creates the protein thyroglobulin which contains tyrosine residues on its chain.
5) It is secreted into the follicles (colloid) and is water soluble.
6) Through iodination reaction iodine is inserted onto tyrosine residues forming T1 (one iodine is attached) or T2 (two iodine atoms are attached). Also catalysed by TPO
7) Conjugation then occurs with an enzyme called Thyroid peroxidase (TPO)
8) Here two ionized tyrosine residues are bound together either two T2 together giving T4 or T1 or T2 forming T3.
9) This mature thyroglobulin molecule is then stored in the colloid until TSH binding to TSH receptor on basolateral membrane.
10) The mature thyroglobulin molecule then enters the cell by endocytosis.
11) The vesicles combine with lysosomes containing enzymes which then remove T3 or T4 from the thyroglobulin (via Proteolysis) forming active thyroid hormones.
12) T3 and T4 are released into the blood stream.
T4 (prohormone) & acts as reservoir for T3 (active thyroid hormone).
13) T4 is mono-deiodinated to T3 by iodothyronine deiodinase (D1, D2, D3) at appropriate tissues (e.g. liver) releasing them and they then diffuse into the blood stream and go to required cells.

44
Q

how are peptide hormones transported in the blood?

A

freely water soluble (hydrophilic)

45
Q

why do steroid and thyroid hormones (amines) need to be transported in the blood?

A

Steroid and thyroid hormones (hydrophobic) need to be transported in blood by carrier protein to:
- increase solubility in blood
- increase half-life (as harder for them to be metabolised)
- create readily accessible reserve in blood.

46
Q

what are specific binding proteins?

A

e.g. Thyroid binding globulin (TBG) and cortisol binding globulin (CBG).

47
Q

what are non- specific binding proteins?

A

e.g. Albumin - loose binding. Aldosterone binds to albumin.

48
Q

what do peptide hormones bind to and what does that cause?

A

bind to G-Protein coupled receptor.
Cell surface receptors (GPCR), activate second messenger cascade. There is phosphorylation of proteins within the cell and the activated proteins bring about a physiological response.

49
Q

what do steroid and amine hormones bind to and what does that cause?

A

hormone passes through cell membrane and binds to intracellular receptors (cytoplasm or nuclear receptor) producing a hormone-receptor complex.
HRC binds to HRE (hormone response element) which results in protein synthesis (transcription translation) and the protein produced causes a physiological response.

50
Q

what are endocrine disorders caused by?

A

Often caused by tumours
Or exogenous administration of hormone

51
Q

what is the treatment for endocrine disorders caused by an excess of hormones?

A

surgical removal of part of gland or removal of tumour or change in dose of hormone

52
Q

what 2 types of endocrine disorders are caused by an deficiency of hormones?

A

1 - primary organ inadequate, tropic hormone - feedback (when its coming from the gland - gland failures)
2 - tropic hormone deficient - Autoimmune organ destruction most common cause e.g. addison disease

53
Q

what is the treatment for endocrine disorders caused by a deficiency of hormones?

A

replacement therapy:
Orally absorbed, long half-life e.g. steroid (corticosteroid), thyroid (thyroxine) hormones.
Injection e.g. GH insulin - peptide hormones needs to be injected into the blood otherwise degraded in gastrointestinal tract.
Peptide hormones have a short half-life in the blood.

54
Q

what are examples of endocrine disorders?

A

GH
excess- acromegaly
deficient- dwarfism
ADH
excess- hypervalemia
deficient- diabetes insipidus
Insulin
excess- coma
deficient- diabetes mellitus