38. Hypothalamus and Pituitary

Question 1

List some things that the hypothalamus regulates.

Describe the 2 parts of the pituitary gland, including what they secrete.

Give an example for each hypothalamic nuclei (number) in the picture (showing possible paths of hormone release from the hypothalamus to pituitary)

Answer 1

Pituitary function, feeding, stress response, water balance, sleep-wake cycle, thermoregulation, emotions

Anterior lobe: glandular part, produces growth hormone, TSH, LH and FSH (made in same type of cell), PRL (prolactin), ACTH (corticotropin)

Posterior lobe: neural part, produces ADH and oxytocin. Nb: post pit =birght spot on CT

1. Kisspeptin, stimulates GNRH (3) (gondotrophin releasing hormone)

2. GHRH (growth hormone releasing hormone)(released in median eminance)

4. ADH (vasopressin) (imp for kidney fn)

5. oxytocin

Question 2

How is the pituitary reached to operate on?

Describe the location of the piruitary gland.

What is the importance of transcription factors in pituitary development?

What causes cretinism?

Answer 2

Via sphenoid sinus (trans-sphenoidal surgery)

Protrusion off the bottom of hypothalamus at base of brain. Rests on hypophysial fossa of sphenoid bone in the center of the middle cranial fossa and is surrounded by a small bony cavity (sella turcica). Optic chaism above it. If squashed can cause bitemporal hemianopia.

Has DNA binding ability and means that pituitary cells than can become diff cells depending on the TF e.g. can become a POMC ir TSH cell.

Severe dwarfism becuase Pou1f1 transcription factor mutation (normally makes growth hormone, TSH and PrL = hypothyroidism). Newborn h**eel prick imp for picking up abnormal TSH - can treat with T4 and avoid cretinism development.

Question 3

Describe the 5 pituitary hormone systems.

Answer 3

1) GHRH -> GH -> IGF-I (inhibited by somatostatin)
2) TRH (thyrotropin releasing hormone) -> TSH -> T4 and T3 (inhibited by somatostatin). Also TRH -> PrL
3) Dopamine negatively regulates PrL -> milk glands and immune system
4) CRH, AVP -> ACTH (adenocorticotrophic hormone) -> cortisol
5) Kisspeptin, GnRH -> FDH, LH -> sex steroids, inhibin, ovulation, spermatogenesis

Question 4

Describe the production (and feedback) of thyroid hormones.

Describe the production (and feedback) of growth hormones.

What is the role of GHRH? (Growth hormone release hormone)

Answer 4

TRH -> TSH -> thyroxine (T4, prohormone) -> liothyronine (T3). T4 inhibits TSH and TRH.

GHRH -> GH -> IGF. IGF -ve fb to GH, GHRH. Somatostatin (stim by GHRH and GH) -ve fb to GH an GHRH. GHRH also inhibited by self.

GH conc decreases after puberty

“4 messages from 1 messenger”: increase GH cell number and GH synthesis, stimulate GH release, promote GH cell clusters for coordinated responses

Question 5

Describe:

a) primary underactivity of the thyroid
b) secondary underactivity of the thyroid

Answer 5

a) damage to thyroid e.g. Hashimoto’s thyroiditis (organ-specific autoimmune disease with destruction of thyroid epithelial cells) or a tumor -> hypothyroidism. Results in increase in TRH, TSH and prolactin, and low T4
b) damage to pituitary gland e.g. tumour/radiation. No TSH, so low T4 and organ not very big. TRH increase (but can’t measure). Prolactin low.

Question 6

Describe:

a) primary overactivity of the thyroid
b) secondary overactivity of the thyroid

Answer 6

a) ‘Hot nodule’ - usually benign tumor of thyroid (too much T4 made) OR multinodular goitre. Graves’ disease (auto-antibody with stimulatory activity when it binds to TSH receptor on thyroid cells) -> if long lasting, thyroid burns out. Signs: goitre and eyes come forward. Low TSH (undetectable) and TRH (can’t measure).
b) Pituitary tumour = too much TSH, T4 increase and bigger thyroid gland (goitre). If TSH not supressed (should be if T4 increase) get help.

Question 7

What type of receptor is a GHRH receptor? What happens if there’s a mutant alpha subunit?

What is McCune–Albright syndrome? What are the diagnostic criteria?

When is there the biggest growth hormone release in 24hrs in children?

Answer 7

GPCR - 2 functions: stimulate adenyl cyclase and stop own function (-ve feedback). Mutant alpha SU: constant adenyl cyclase activation - can’t turn self off.

Mosiac mutation, not inherited. Due to chance mutation during development -> mutated cell proliferates -> migrate and expand -> somatic mosaicism (phenotype determined by location and timing of occurance of mutation). DC: fibrous dysplasia, abnormal bones (tumour), cafe au lait spots, endocrine dysfunction (hyperthyroid goitre, adrenal hyperplasia)

At night

Question 8

What is Cushing’s Syndrome?

What is Addison’s disease?

What is the circadian rhythm of cortisol?

How can LH and FSH be made it the same cell and released by the same stimulus but with 2 different consequences?

Answer 8

Excess glucocorticoid hormones in body - cotisol excess. Due to pituitary or adrenal cortex adenoma, OR excess glucocorticoid steroids e.g. prednisolone. Complications incl. diabetes, osteoporosis, depression, muscle weakness immunity decrease

Coritsol insufficiency. Slow onset symptoms, may include abdo pain, weakness, weight loss

Increase when wake up, decrease throughout day (increase a little after food) and increase at night

GNRH goes in pulses. If fast (1/hr) mainly have LH and not much FSH; if slow (3/hr) mainly FDH and not much LH