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52 Cards in this Set

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Introduction - structure of anterior/posterior pituitary

• Anterior – true endocrine gland made of glandular epithelium.




• Posterior – downgrowth of hypo and remains joined to the hypothalamo-hypophyseal nerve tract and secretes neurohormones made in hypothalamus.

What is common in their synthesis? Preprohormone to prohmone

• Peprohormone (large inactive protein from ribosome) contains copies of a peptide hormone, e.g. a signal sequence that directs protein to RER. N-terminal signal sequence cleaved and– prohormone – transported to ER for packaging.

What is common in their synthesis? Prohormone to release

• Golgi – packaged into membrane-bound secretory vesicles with proteolytic enzymes – cleaved to activate hormone – post-translational modification.




• Secretory vesicles containing peptides are stored in cytoplasm of endocrine cell until cell receives signal for secretion.




• Vesicles move to cell membrane and release their contents by Ca-dependent exocytosis.




• All peptide fragments released together into ECF – co-secretion.

Explain the synthesis of posterior hormones

• Synthesised in hypothalamus, packaged in granules with the transport protein neurophysin I (associated with ADH), II (associated with oxytocin)

How are posterior hormones stored

• Granules transported to terminals of axons in posterior and stored in axon terminals or Herring bodies along axon.

How are posterior hormones released

• Stimuli in form of nt released for hypo interneurons – neurones depolarise and propagate AP down axon, - granules secreted (along with neurophysin) by Ca-dep exocytosis and contents diffuse into adjacent capillaries as free hormones. Act on target – G protein-linked receptors.

Explain the synthesis of thyroid hormones

Hormones (T4 and T3) produced by follicular cells of thyroid


Coupling of iodinated tyrosine (iodination by thyroid peroxidase) to form thyroid.




Intracellular enzymes separate 3&4 – circulation.

How is anterior hormones secretion regulated?

• Hormone secretion controlled by hypothalamic neurohormones. All hormones except prolactin have another endocrine gland/cell as target – tropic. Trophic hormones – direcly affect growth – hyperplasia/hypertrophy.

How are RH made and how do they travel from hypothalamus to anterior pituitary?

• RHs synthesised in neurones of hypothalamus travel down axons and diffuse into primary plexus of hypophyseal portal system. Carried by hypophyseal portal veins to secondary plexus – distributed to target cells within anterior pituitary.





Where are anterior synthesised, stored and secreted?

Cells in anterior pituitary NOT hypothalamus.

What is the structure of posterior hormones and their targets?

Oxytocin (nonapeptide)– - Uterus, mammary glands




Vasopressin (nonapeptide dis. 1,6)- Kidneys or Arterioles

Where are posterior hormones synthesised?

Cell bodies of large neurones within supraoptic and paraventricular nuclei in hypothamalus





What is the effect of oxytocin?


How is its action mediated?

Smooth muscle contraction


Uterine contractions; lactation – contraction of myoepithelial cells lining duct of mammary gland – pos feedback




Mediated via specific receptors on target cells linked to IP3



What is the effect of ADH?

Stimulates water retention (V2 receptors, cAMP) in collectin ducts




Raises BP - vasoconstriction (acts on V1A receptors – via Ca, PLC and IP3)


induces male aggression

What is the structure of anterior hormones, their targets and location of synthesis?

Adrenocorticotropic hormone (ACTH)– Adrenal gland - Corticotrophs




Thyroid-stimulating hormone; Thyroid gland; Thyrotrophs




Follicle-stimulating hormone Gonads Gonadotrophs




Luteinizing hormone Gonads Gonadotrophs




Prolactin Ovaries, mammary glands Lactotrophs




Growth hormone Liver, adipose tissue Somatotrophs

How is Oxytocin regulated?

Activation of nerve endings in nipple/uterus stimulate release.


Neurogenic feedback - reflexes relayed to hypothamalus via spinothalamic tract

How is ADH regulated?

Increase in osmolality (osmoreceptors in hypothalamus)


Fall in ECV of >8%(pressure receptors), CCK secreted by SI

Decrease in arterial pp of O2 and increase CO2



How is ACTH regulated?




Effect of hypersecretion

Controlled by CRH from hypothalamus.


- circadian rhythm: Released episodically from corticotrophs


- stress: surgery and hypoglycaemia


- negative feedback control by cortisol.
















Hypersecretion – Cushing’s. Hyper/hypo-responsiveness of target cell due to upregulation of receptors.

How is TSH regulated?

TSH from anterior pituitary. TSH secretion stimulated by TRH from hypothamalus. Thyroid hormone suppresses TSH secretion.

How is FSH regulated?

Secretion controlled by GnRH.

How is LH regulated?

Secretion controlled by GnRH.

How is prolactin regulated?

Controlled by Pit-1 Tf. Under inhibitory control of dopamine. Released episodically.


Thyrotropin-releasing hormone (TRH) has a stimulatory effect on prolactin release




How is GH regulated?

Release mediated through (+) GHRH and (-) somatostatin – CNS control.




Episodic secretion related to sleep-wake cycle. Peaks every 2-3 hrs.

What are tropic hormones?

Hormones that have other endocrine glands as their target (FLAT)
FSH - maturation of eggs and production of sperm
LH - stimulates release of steroid hormones in gonads - ovary and testes
ACTH - stimulates adrenal cortex to release glucocorticoids
TSH - stimulates thyroid gland to make and release thyroid hormone

How does dopamine inhibit prolactin?

Dopamine produced by neurons in the arcuate nucleus is secreted into the hypophyseal portal system of the median eminence, which supplies the pituitary gland.





How is prolactin produced?

In the absence of dopamine, secreted continuously.

What is the solubility of thyroid hormones?

Lipophilic

Name the releasing hormones

GnRH


TRH, CRG, SS, Dopamine, PRF

How are RH secreted?


What is the effect of RH release?

Pulsatile secretion, entrained to daily and seasonal rhythms through CNS input, signals transduced through Ca/cAMP




Stimulates synthesis of target anterior hormones at transcriptional level, modifies activity – post-transcriptional effects, hyperplasia/hypertrophy of target cells



What are disorders of ADH secretion?


SIADH – excessive release, hypervolemia results in dilutional hyponatremia. Treated with ADH antagonist


Undersecretion – can lead to DI

What are the effects of over/undersecretion of prolactin?

Oversecretion: benign tumour - pituitary adenoma. Spontaneous/lack of suppression in hypothalamic trophic hormone.




Overproduction– Overproduction– infertility. Treated by bromocriptine




Undersecretion – disconnection of axis (tumour), pituitary hypoplasia, pituitary destruction

What other factor could cause prolactin release?

Drugs - due to dopamine antagonist effects

What is the effect of ACTH?

Secretion of glucocorticoid(gluconeogenesis, suppress immune system), mineralocorticoid (ALDOSTERONE, Na/H2O retention,increase blood vol and bp) inadrenal cortex and androgens

What is the effect of TSH?

TSH stimulates cell metabolism, promotesa thropicresponse in cell size and activity




Causes increase in: TM ion fluxes, iodination of thyroglobulin, cellular metabolism, DNA synthesis, iodine flux into cell




T3 binds receptor. T4 deiodinated in target cells to T3. T4 binds to serum proteins.

What is the effect of FSH?

Growthof reproductive system

What is the effect of LH?

Sexhormone production

What is the effect of Prolactin?

Secretionof oestrogens/progesterone; milk production – neuronally mediated.

What is the effect of GH?

Promotes bone, soft tissue and viscera growth; lipid and carbohydrate metabolism




Indirect: stimulated liver toproduce somatomedins




Lipolysis

What is the mechanism of action of thyroid hormones?

Hydrophobic so pass through membrane


Receptors in nucleus of target cells


Forms homo/heterodimers with receptor - binds DNA upstream of regulated gene at hormone responsive element (HRE)







Effect of thyroid hormone

Determines BMR - increases conc. enzymes in catabolism, T3 interacts with catecholamines to increase HR and force of contractions

Regulates growth

Other than GH, what hormones are involved in growth?

· Thyroid hormone – hypersecretion not excessivegrowth


· Insulin – hyper – excessive growth


· Androgens – puberty, stimulate protein synth.Effect depends on GH


· Estrogens – effects growth prior to bonematuration

What is the structure of the thyroid gland?

· Highly vascularised


· Functional units – follicles – change appearanceaccording to activity


· Follicles – epithelial cells surround colloidfilled lumen, serves as EC storage for hormones

Cause for ADH secretion?

Vasopressin is secreted from the posterior pituitary gland in response to reductions in plasma volume, in response to increases in the plasma osmolality, and in response to cholecystokinin (CCK) secreted by the small intestine:

Explain the stimuli for ADH release and the mechanism for its effect

1) Most Potent: Osmolarity. Greater than 280 mOsM Hypothalamic osmoreceptors Interneurones in hypothalamus - synthesise AD. Released from pituitary. Collecting duct epithelium.




2) Low blood volume Decreased atrial stretch detected by stretch receptors. Sensory neuron to hypothalamus.






3) Decreased blood pressure. Carotid and aortic baroreceptors. Sensory neuron to hypothalamus.

Oxytocin regulation

neurogenicfeedback. Spinothalamic tract

Cortisol regulation

releasedby stress and circadian rhythm.

Prolactin :

oe/prosecretion, milk production, TSH/ACTH secretion. TRH stimulatory effect. Inhibitedby dopamine produced in arcuate nucleus into portal system of median eminence. Undersecretion – disconnection of axis, pituitaryhypoplasia

GHregulation+ function

+GHRH, Liver produces somatomedins stimulating somatostatin from hypothalamuswhich inhibit release of GH. Lipolysis.

Trophichormones

–induce hypertrophy or hyperplasia. TSH and ACTH

RH

pulsatile. Affect transcription

Thyroid

T3 interacts with catecholamines to increase HR and force ofcontractions.

ADH

plasmavolume – arterial stretch receptors, osmolarity (280 mOsM) by hypothalamicosmoreceptors, pressure – carotid/aortic baroreceptors. CCK from SI.