Endocrinology intro (1)

Question 1

Cell communication: comparison of hormone vs nervous system control

Answer 1

Nervous communication: fast, rapidly modulated message:

cells communicate electrically by precise, defined fibres, NTs, & effector cells

Hormones: provides a slower developing, widespread regulatory action:

(endocrine, paracrine, autocrine, neuroendocrine, neurotransmitters, exocrine)

Question 2

Types of hormone secretion

Answer 2

(see diagram in notes)

• endocrine: from cell to blood stream and can bind to relevant receptors anywhere in the body

-neuroendocrine nerve cell to blood stream

-paracrine: secretion has local effect e.g. secretion into digestive tract

-neurotransmitters: transmit messages between neurons and between neurons to muscles

• autocrine: effect on the cell that produces

(We’ll be focusing on endocrine in these lectures)

Question 3

Endocrine system

Answer 3

Made up of ductless glands scattered through the body that secrete hormones which travel in blood to target cells

–Targets cells have specific receptors for hormone
–Regulate or direct particular function

Two hormone groups (classified according to their solubility)

Hydrophilic:
*Peptide hormones
*catecholamines

Lipophilic:
*Steroid hormones
*Thyroid hormones

Question 4

Hormones

Answer 4

Endocrine cell secretes hormones ->
plasma hormone is:
excreted
THEN
inactivated by metabolism
OR
activated by metabolism/ catalyses hormone formation
resulting in actions on target cells

*Plasma levels of hormones are controlled by change in rate of secretion

*Direct regulatory inputs influence secretory output:
-Neural input
-Other hormone

*Effective plasma levels also affected by:
-Activation
-Metabolism/clearance

Question 5

Major endocrine glands

Answer 5

See diagram
- hypothalamus
-pituitary gland
-thyroid gland
-adrenal glands
- pancreas
- ovaries/testes

Question 6

Hormone receptor interaction

Answer 6

Hormones have specificity

Many drugs block receptors (antagonistic) or are agonists and enhance receptor response
*lock and key hypothesis
*complimentary chemical configuration
*confers control / specificity
*drug actions

Question 7

Hydrophillic hormones have extracellular receptors

Answer 7

hydrophilic hormones cannot pass through the lipid membrane so they require extracellular receptors to convey the message to the inside of the cell.

see diagram in notes: Pictures 1-3 show hydrophillic hormone and picture 4 shows lipophillic hormone action:

1 – by activating an ion channel

2- by direct control of effector enzyme

3- by indirect (G-protein) coupling via second messengers/ ion channels

4- lipophilic hormones can go straight through the membrane to bind to a receptor in the nucleus or elsewhere in the cell

** much more goes on in the cell these diagrams are simplified**

Question 8

Signal transduction

Answer 8

Signal -> receptor activation

Transduction is the process where stimulus is turned into response

Transduction pathways available:
a) by activating an ion channel
b) by direct control of effector enzyme
c) by indirect (G-protein) coupling via second messengers/ ion channels

Question 9

Steroid hormones

Answer 9

Steroid hormones (lipophilic) have intracellular receptors:

*Hormones circulate bound to carrier proteins

*Free hormone can pass through membrane to receptor
-Activation occurs
-Dimer binds to specific regions of DNA changes in gene expression: mRNA produced
-Relevant protein synthesised: response

-Lipophilic hormones can move through the plasma membrane but are relatively insoluble in plasma fluid so they often require carrier proteins to move around

• medically, free and bound percentages of the hormone are important – a lack of binding carriers can lead to hormone overload and disease

Question 10

Synthesis of peptide hormones

Answer 10

• synthesised as a large pre- hormone and small parts split off into pro-hormone
• pro-hormones tend to be packaged and small sections are divided off as hormones
• hormones are stored in vesicles and secreted when triggered

In type 2 diabetes there is no stored insulin so first phase is lost

Question 11

Comparison of steroid and peptide hormones

Answer 11

Steroids aren’t stored and are made on demand

Peptides can’t enter the cell (need an extracellular receptor) and are rapidly broken down – short half-life (minutes), impact minutes to hours

– peptides are stored and released as required

Steroids are broken down more slowly, as they are lipid soluble receptors are within the cell – long half-life (hours), impact hours to days

-Steroids aren’t stored and are made on demand

property/ peptide/steroid (see notes for table)

Synthesis
p- Stored as inactive precursor
s- Usually not stored made on demand

Cell membrane permeability
p-Water soluble unable to cross
s- Lipid soluble pass easily- diffusion

Receptors
p -Membrane bound extracellular
s- Intracellular

Transport
p- In solution in blood
s- Poorly soluble- bound to plasma proteins

Metabolism
p- Rapidly broken down
s- Slowly degraded

Half-life
p- Short (mins)
s- Long (hours)

Duration of effects
p- Mins-hours
s- Hours-days

Question 12

Hormones and homeostasis

Answer 12

*Hormones contribute to homeostasis

*To maintain homeostasis control systems need to:
-Detect changes
-Integrate information from sources
-Make adjustments to restore the “normal” situation

*Two groups of control system:
-Intrinsic – local control – within organ
-extrinsic – further away – external to organs impacting multiple organs

Question 13

Control systems

Answer 13

*Feedforward:
Action taken in anticipation of a change
e.g. salivation (Pavlov’s dog) and digestive stimulation in advance of food
(from thinking about it etc.)

*Feedback:
Response made after detecting a change in the system

Two types: negative and positive
e.g. pos - in pregnancy oxytocin encourages more oxytocin release

Question 14

Control of hormone secretion

Answer 14

Most hormones are released episodically (in short bursts) eg. circadian rhythm (24hr cycle)

For example: cortisol level rises approx. 2 hours before you usually get up in a 24 hour cycle

Circannual rhythms also exist (year cycle) e.g. flower blooming, breeding cycles in most animals

For example: Sparrow testicles get larger may – august breeding season

Other hormones are produced on demand rather than according to a rhythm

Mechanisms of control:
-control by other hormones
-control by neurons
-control by plasma levels of nutrient or mineral eg insulin in response to glucose levels

(^ also influenced by rate of activation or metabolic inactivation, excretion, binding to plasma proteins)

Question 15

Feedback in control of hormonal systems

Answer 15

negative feedback:
Acts to damp hormonal response ie extremes of hormone concentration are limited
alters the plasma concentration of a hormone in a direction opposite to that of previous change

Positive feedback:
Initial change in system starts a sequence of events that leads to further disturbance

Hypothalamus and pituitary gland anatomy:
Hypothalamus is a down-growth of the brain full of neurones the pituitary descends below this

Question 16

Connection between hypothalamus and pituitary

Answer 16

*Axons from 2 groups of hypothalamic neurons pass down the infundibulum and end in posterior pituitary

*no important neural connections between hypothalamus & anterior pituitary but these areas are connected by blood vessels

*Capillaries at base of hypothalamus, the medidan eminence, recombine to form the hypothalamo-pituitary portal vessels.

*The short portal vessels connect anterior with posterior pituitary

Question 17

Releasing hormones aka releasing factors

Answer 17

Secretion of each anterior pituitary hormone is stimulated or inhibited by one or more hypothalamic hypophysiotropic hormones (more detail in next lecture)

Hormone/ Effect on Anterior Pituitary

Thyrotropin-Releasing hormone (TRH)
Stimulates release of TSH

Corticotropin-Releasing hormone (CRH)
Stimulates release of ACTH

Gonadotropin-releasing hormone (GnRH)
Stimulates release of FSH and LH

Growth-hormone releasing hormone (GHRH)
Stimulates release of growth hormone

Growth-hormone inhibiting hormone (SS) somatostatin
Inhibits release of growth hormone and TSH

Prolactin-releasing factors (PRF)
Stimulate release of prolactin

Dopamine (prolactin inhibiting hormone)
Inhibits release of prolactin

Question 18

Control of hormone secretion from anterior pituitary by hypothalamic releasing hormones

Answer 18

*Releasing hormones are synthesised in neurons of hypothalamus

*Neurons terminate in median eminence around capillaries that are origins of hypothalamo-pituitary portal vessels

*Action potentials cause release of hormones into portal vessels which are carried to anterior pituitary

(see diagram)

Question 19

Other control of the HP axis

Answer 19

*Neural
Hypothalamus receives inhibitory & excitatory input from CNS.
Stimuli include: pain, sleep, emotion, fright, light etc

*Other hormones
Other hormones can influence secretion in a positive or negative way:
-Permissiveness – one hormone allows another hormone to act
-Synergism – additive effect
-Antagonism – inhibitory effect

Question 20

Major types of endocrine disorder

Answer 20

*Hypersecretion: can be primary or secondary

*Hyposecretion: can be primary or secondary

*Hyperresponsiveness of target cells due to an upregulation in receptors or increase in number

*Hyporesponsiveness ie decreased response of target cells, due to down- regulation or low distribution of receptors

Question 21

What affects action of hormones?

Answer 21

-Quantity of hormone and quantity of receptors

-Testosterone in its active form causes hair growth according to receptor distribution and number – hence why some men have hairy chests

Question 22

Endocrine disorder example: Cushings syndrome/ Cushings disease

Answer 22

CRH (hypothalamus) -> ACTH (anterior pituitary) -> Cortisol (adrenal)

primary production of excess cortisol by the adrenals or secondary hypersecretion of ACTH resulting in increased cortisol

Cushings syndrome = anything causing elevated cortisol

Cushings disease = high levels of cortisol due to hypersecretion of CTH due to pituitary tumour

Type 2 diabetes usually due to insulin resistance – insulin is produced but not responded to = hyporesponsiveness (linked to inflammation)

Question 23

Posterior pituitary hormones:
Hormones of the neurohypophysis: Representation of structural relationships in posterior pituitary

Answer 23

*The posterior lobe of the pituitary develops as a downgrowth from the hypothalamus and remains joined to this by the hypothalamo-hypophysial nerve tract.

*Hormones synthesised within cell bodies of large neurons lying in supraoptic and paraventricular nuclei of the hypothalamus

^Hormones are synthesised in the bodies of large neurones located in thehypothalamus and released from the dendritic ends of these neurones - located in the posterior pituitary and therefore commonly referred to as posterior pituitary hormones.

Question 24

Posterior pituitary hormones

Answer 24

*Oxytocin
*Vasopressin aka ADH or AVP affects blood vessel dilation
^ They are both nonapeptides with disulphide bridge linking amino acids 1 and 6 to form a ring

*Hormones are synthesised in the hypothalamus, packaged in granules with a larger protein called neurophysin which acts as a transport protein.
*Granules are transported down the fibres to the terminals of axons located in posterior pituitary.
*When the neurons are stimulated, granules released & contents diffuse into adjacent capillaries.

*Prior to secretion, hormones are stored in secretory granules in terminals themselves or Hering bodies along the length of the axons.
*Both oxytocin and vasopressin are secreted by calcium-dependent exocytosis similar to the secretion of NTs at other nerve terminals.
*Once released they circulate in the blood as free hormones. (1/2 life: few minutes)

*Kidneys, liver & brain are main sites of clearance.

*Both act on their target glands by G protein-linked cell surface receptors

Question 25

Oxytocin

Answer 25

*Causes contraction of smooth muscle
–uterus during labour
–myoepithelial cells lining duct of mammary gland stimulating milk ejection

*Example of positive feedback -production of oxytocin stimulates more production – until the original signal ceases
*Ferguson reflex

*Two main sites of action
-uterus – stimulated during intercourse
-mammary gland -Stimulation of the nipple triggers oxytocin triggering milk release in lactating females

^Baby crying triggers feedforward (as on graph) suckling drives release

*Its action is mediated via specific receptors on target cells linked to IP3 second messenger system.

*Clinical disorders of oxytocin secretion are rarely encountered

*Synthetic oxytocin is used clinically in injections to induce labour and also to stimulate uterus after delivery to lessen the risk of uterine haemorrhage

*(interesting role in bonding/neuropsychology)

Question 26

Control of oxytocin secretion

Answer 26

*Circulates in v low concentrations, normally undetectable

*elevated during parturition, lactation and mating

*Activation of nerve endings in nipple and uterus stimulate release of oxytocin.

These reflexes (relayed to the hypothalamus via the spinothalamic tract) are good examples of neurogenic feedback control mechanisms

*Neurogenic = developed within the nerves

Raspberry leaf tea – stimulates contractions – speeds up labour: theory : it may lower progesterone increasing muscle tone

Progestrone levels are high during pregnancy preventing uterine contractions which could result in labour. Braxton Hicks ‘practice contractions’ occur in the final few weeks of pregnancy so it is likely that the raspberry leaf tea by lowering progestrone increases the amount of practice contractions therefore improving muscle tone for labour

**raspberry leaf can therefore cause miscarriage and is not safe except in the last 6 weeks of pregnancy

Question 27

Vasopressin and its receptors

Answer 27

*Two main functions:
-control of water excretion
-regulation of blood pressure (vasoconstrictor)

*Acts through specific receptors on plasma membrane of target cells. Situated in many organs.

Axons of vasopressin cell bodies project to the posterior pituitary, the median eminence portal sytem. spinal cord & other brain centres

Vasopressin receptors:
*V1 – all tissues except the kidney, IP3 second messenger system
*Vasopressor action (V1A & V1B)
*V2 – Kidney, cAMP as second messenger
*Affects water uptake
(see last years notes on kidneys)

Question 28

Control of ADH release

Answer 28

Factors stimulating release

*increase in osmotic pressure of blood
*fall in ECV (effective circulating volume) of >8%
*dec in arterial pp (partial pressure) of O2 & inc in arterial pp of CO2

e.g due to haemmorhage or suffocation
or
*other hormones
*drugs
*CNS

Question 29

Disorders of vasopressin production

Answer 29

overproduction of vasopressin (SIADH)
*caused by:
brain disorders such as trauma, infection, malignant disease, also drug treatment with antidepressants/ antipsychotics.
*results in:
retention of water, serum hypo-osmolality, hyponatraemia and v high urine osmolality
*symptoms:
headache, apathy, nausea, vomiting, neurological malfunction, impaired consciousness. Can lead to coma and fatal convulsions
*treatment:
surgery (if tumour), restrict fluid intake, replace sodium,administer AVP antagonist eg demeclocycline

Undersecretion of vasopressin
*Hyposecretion of ADH caused by damage or dysfunction of the hypothalamus can lead to diabetes insipidus
*Often as a result:
of head injury or tumour, or can be caused by autoimmune destruction of vasopressin neurons
*patients cannot reduce the flow of urine when deprived of water and hence plasma osmolality increases.
*(don’t confuse with nephrogenic type DI, failure of kidneys to respond or psychogenic polydipsia)

*symptoms:
polydipsia (drinking a lot), polyuria (producing a lot of urine)
*diagnosis:
deprivation of water whilst recording osmolarity of blood and urine output
*treatment:
synthetic vasopressin or analogues