L6 - Intro to the HPA axis

Question 1

ANATOMY OF THE PITUITARY GLAND

i) what type of circulation exists between the hypothalamus and ant pit?
ii) what lines this circulation? what does this allow?
iii) what are the embryological origins of the anterior and posterior PG?
iv) where does the PG sit? which bone is this in?
v) which part of the PG is endocrine and which is neuroendocrine?

Answer 1

i) portal sinusoidal circulation

ii) sinusoids (not endothelium) which have pores in
- this allows molecules to disperse to tissues

iii) ant pit from oral cavity (rathkes pouch) and post pit from the diencephalon
iv) PG sits in the sella turcica in the sphenoid bone
v) anterior is endocrine and posterior is neuroendocrine

Question 2

HYPOTHALAMUS AND HORMONES

i) integrates function that control which two homeostatic mechanisms?
ii) which system does it function with?
iii) which area releases hypothalamic hormones?
iv) what do these hormones control the secretion of in the PG? (5)

Answer 2

i) temperature and chemical homeostasis
ii) functions with the limbic system
iii) median eminence releases small peptides and dopamine
vi) control secretion of gonadotropes, lactotropes, corticotropes, thyrotropes and somatotropes

Question 3

HYPOTHALAMIC RELEASING HORMONES

i) name the 6 HT releasing hormones
ii) what action does each have?

Answer 3

1) Gonadotrophin RH
- stimualtes FSH and LH release from ovaries/testes

2) somatostatin
- inhibits GH secretion

3) dopamine
- inhibits prolactin secretion

4) Corticotrophin releasing factor (CRF)
- stimulates ACTH secretion from PG

5) thyrotropin releasing hormone (TRH)
- stimulates TSH release from the PG

6) Growth hormone releasing hormone
- stimulates GH secretion

Question 4

HYPOTHALAMO-HYPOPHYSEAL AXIS

i) how are hormones delivered from the HT to the ant PG?
ii) cell bodies from the HT project to the post PG and stimulate production of which two hormones?

Answer 4

i) via a portal sinusoidal system
ii) cell bodies project to the post pit and stimulate release of oxytocin and ADH

Question 5

HYPOTHALAMIC-PITUITARY AXES

i) explain the sequence of each axis
- what is released from the HT?
- what cells are activated in the PG?
- what does the PG then release?
- what target organ does this have effects on?

1) adrenal pit axis, 2) thyroid pit axis, 3) gonado pit axis, 4) growth hormone axis, 5) lacto pit axis
ii) name the six main hormones released from the ant PG

Answer 5

Adrenal pit axis - CRH is released from the HT
- PG corticotropes release ACTH which causes adrenals to produce cortisol

Thyroid pit axis - TRH is released from the HT
- PG thyrotropes releases TSH which causes thyroid to produce T3 and T4

Gonado pit axis - GnRH released from HT
- gonadotropes release LH and FSH which stimulate the testes to produce testos and ovaries to produce oestrogen

GH axis - GHRH released by HT (inhibited by somatostatin)

• somatotropes in PG release GH acts on liver to make IGF1
• somatostain and GHRH balance to control release of GH

Lacto pit axis - HT produces DA
- DA inhibits prolactin secretion from lactotropes

Question 6

CELLS OF THE ANT PIT GLAND

i) name each cell type and what they synthesise (5)
ii) which cell type makes up the biggest proportion of cells?

Answer 6

1) somatotropes - synth growth hormone
2) lactotropes - synth prolactin
3) thyrotropes - synth TSH
4) gonadotropes - synth FSH and LH
5) corticotropes - synth ACTH
ii) somatotropes make up ~50% of all ant pit cells

Question 7

GROWTH HORMONE

i) what is the character of its secretion from the PG?
ii) what can be used of as a marker of GH status? where can this be found?
iii) which hormone is a negative regulator of GH?
iv) what does its half life vary between?
v) what effect does GH have on bone and tissue?
vi) when is most GH secreted? what does this aid in?
vii) what two additional effects can GH have on fat and muscle?

Answer 7

i) pulsatile secretion
ii) use IGF1 made by the liver
iii) somatostatin
iv) between 6-20 mins
v) aids growth of bone and tissue - keeps muscle in good shape
vi) most GH is secreted at night and aids regeneration
vii) GH can act on protein synthesis as well as have metabolic effects

Question 8

PROLACTIN

i) how many aa is it and which cells synthesise it?
ii) what is its major function?
iii) what inhibits its release?
iv) irritation of which anatomical area will increase prolactin secretion? why?
v) what effect does it have on gonadal function? how does it do this?

Answer 8

i) 199 aa sequence and synth by lactotropes in ant pit
ii) functions in milk production
iii) inhibited by dopamine
iv) irritation of the pituitary stalk will increase prolactin because its negatively regulated by DA from the HT (if DA cant reach ant pit then PRL will be disinhibited)
v) inhibits gonadal function by dampening the ovaries (reduces fertility postnatally while breastfeeding)

Question 9

ACTH AND ADRENAL GLANDS

i) is the adrenal medulla affected by ACTH?
ii) what are the three layers of the adrenal cortex? what class of steroid hormone does each layer produce?
iii) what is the pattern of release of cortisol? name a situation it may be high in

Answer 9

i) no

ii) zona glomerulosa - produces MCs
zona fasciculata - produces GCs
zona reticularis - produces androgens

iii) cortisol has diurnal variation (high in am and low in pm)
- high in stressful events

Question 10

FSH/LH & THE GONADAL AXIS

i) what type of proteins are FSH and LH?
ii) are they long or short pps? what groups are they usually bound to?
iii) what does LH predominantly control? what does FSH predominantly control?
iv) at what point in the menstrual cycle is there a surge of FSH and LH?
v) what two things do FSH and LH control in males? which predominantly controls which?

Answer 10

i) glycoproteins
ii) long pp chains bound to carbohydrate groups

iii) LH controls oestrogen production > egg production
FSH controls egg production > oestrogen production

iv) surge of LH and FSH at ovulation (mid cycle)

v) males - LH controls testos prod > sperm prod
FSH controls sperm prod > testos prod

Question 11

POSTERIOR PITUITARY

i) what type of tissue is it?
ii) which nuclei project axons from the HT to the post pit? (2)
iii) which tract do axons pass from the HT to the post pit?
iv) where are post pit hormones synthesised? then where do they travel?
v) how are hormones stored in the post pit before they are released?
vi) what are the two principal hormones produced by the post pit? what structure do they have?

Answer 11

i) neuroendocrine
ii) supraoptic and paraventricular nucleus
iii) axons pass down the hypothalamohypophyseal tract
iv) hormones are synth in the cell bodies of neurons in the supraoptic and paraventric nucleus then travel down axons to the post pit
v) hormones are stored in vesicles in the post pit before being released
vi) Post pit produces ADH and oxytocin = peptides

Question 12

ADH

i) what two things does it control? what effect does it have on each?
ii) what effect does it have on the collecting duct?
iii) which receptors does it bind to for hormonal actions?
iv) what effect does it have on vascular smooth muscle cells? what receptors mediate this non hormonal action?

Answer 12

i) controls water balance and BP
- reabs water from urine in times of dehydration
- vasconstricts vasc smooth muscle to increase BP

ii) increases permeability of the CD to water by insertion of AQPs
iii) binds to V2 receptors for hormonal action (on aquaporins)

iv) constricts vascular smooth muscle cells (non hormonal)
mediated by V1 receptors

Question 13

OXYTOCIN

i) what role does it play in breastfeeding? which cells are involved in this?
ii) what effect does it have on uterine smooth muscle during childbirth?
iii) what type of feedback mechanism is involved in its regulation? explain in relation to breastfeeding and childbirth
iv) what type of receptor class does it activate? what does this subsequently lead to?

Answer 13

i) allows ejection of milk by contracting myoepithelial cells of alveoli
ii) causes contraction of uterine smooth muscle during childbirth

iii) positive feedback
breastfeeding - suckling on nipple influences HT which causes more oxytocin release which causes more milk ejection
childbirth - foetus drops in uterus which stim cervical stretch which causes oxytocin prod which causes uterine contracs
uterine contracts pos feedback to cervical stretch which causes more oxytoxcin release

iv) activates GPCRs which causes calcium release and muscle contraction (in breast and uterus)

Question 14

LESIONS IN THE HPA AXIS

i) what two areas may the disease lie?
ii) what is the most common cause of lesions in the axis? give four examples of things that fall into this category
iii) name four congenital embryopathic defects
iv) what are the most rare defects that result in lesions of the axis?

Answer 14

i) hypothalamus (HT or pit stalk) or pituitary gland

ii) acquired defects
- tumours, trauma, inflammatory/infiltrative and vascular (apoplexy)

iii) Kallmans syndrome, ancephaly, pituitary aplasia, midline defects (fail to grow and thrive)
iv) genetic defects are rare (in HT or PG hormone gene or receptor)

Question 15

CLINICAL MANIFESTATIONS OF HPA LESIONS

i) what symptoms do mass effects cause? why? (2)
ii) what two endocrine effects can lesions cause?
iii) what is the syndrome of progressive loss of anterior PG function? which hormone is the first to stop working?
iv) hypopituitarism with DI is suggestive of what type of aetiology? why?
v) what is the most common type of pituitary tumour?

Answer 15

i) headaches and visual disturbance do to compression of structures
ii) hypo or hyperpituitarism
iii) panhypopituitarism - FSH and LH are lost first
iv) hypopit with DI suggests a hypothalamic aetiology as DI is a disorder of ADH and HT produces ADH
v) prolactin secreting

Question 16

PITUITARY ADENOMA

i) what are the two types and their measurements?
ii) are they usually mono or polyclonal?
iii) what symptoms do prolactinomas cause? (2)
iv) what syndrome can be caused by ACTH secreting tumours? give three symptoms
v) what syndrome from GH secreting tumours produce?
vi) are mass effects and hypopitiutiarism linked to functional status?

Answer 16

i) micro < 10mm and macro >10mm
ii) usually monoclonal
iii) galactorreah (milk prod from breast) and reduced gonadal function

iv) cushings (excess cortisol)
- central obesity, osteoporosis, thin skin, diabetes

v) GH can produce acromegaly (adults) or gigantism (children)
vi) mass effects etc can be independent of functional status ie whether the tumour is hormone secreting or not

Question 17

CLINICAL ASSESMENT OF PIT ADENOMAS

i) what would you look for in the history and examination?
ii) which basal hormones would be tested? (2)
iii) what secretion test can be carried out? give an exmaple
iv) what imaging modality may be used?

Answer 17

i) signs of hormone excess or deficiency eg have hands/feet grown
ii) pit hormones eg prolactin, ACTH, GH AND downstream hormones eg IGF1 and cortisol
iii) stimulated secretion eg insulin hypoglycaemia test
iv) CT

Question 18

INSULIN HYPOGLYCAEMIA TEST

i) what is the logic behind this test in regards to PG hormones and hypoglycaemia?
ii) in a normal individual - what happens to plasma cortisol and serum GH on admin of insulin (induced hypogly)
iii) what happens to plasma cortisol/GH in patients with hypopituitarism?

Answer 18

i) when blood sugar is low, PG hormones (GH and cortisol) are released to bring it back up - good way to check normal functioning of PG hormones
ii) normally on admin of insulin, get hypogly then brief and brisk increase in cortisol and GH in the blood
ii) if hypopit - there is no increase in cortisol/GH post insulin admin

Question 19

BILATERAL INFERIOR PETROSAL SINUS & PERIPH VEIN SAMPLING

i) what hormone does this test sample?
ii) how is it set up?
iii) what hormone is given to induce production of the hormone being tested?
iv) what can this show about laterality of the tumour?

Answer 19

i) samples ACTH and whether the tumour is secreting ACTH
ii) two catheters into veins that supply the PG and use them to sample hormone levels
iii) give CRH which causes ACTH to be produced from the PG and if the tumour is ACTH secreting then there will be a sharp rise in ACTH
iv) catheters in each vein so the vein with the highest increase in ACTH can show location of tumour

Question 20

PIT TUMOURS AND VISUAL FIELDS

i) which part of the visual system sits above the pituitary gland?
ii) what type of visual disturbance is commonly seen in pit tumours?
iii) which image does this correspond to?

Answer 20

i) optic chiasm
ii) bitemporal heminopia (tunnel vision)
iii) corresponds to image 2