lecture 6: HPG axis Flashcards
1
Q
summary of hypothalamo-pituitary gonadal axis?
A
- start off where the CNS feeds into the hypothalamus
- gives signals which lead to the release of factors
- these factors regulate the pituitary
- regulates, through LH and FSH, the ovary and testis
- hormones from these gonads affect the accessory sex organs
- so on
2
Q
how does the pituitary develop?
A
- dual embryological origin
- roof of pharynx → anterior pituitary
- neural outgrowth → posterior pituitary
- therefore part epithelial in origin and part neural in origin
- “master endocrine gland” regulates reproduction, metabolism, growth, stress response etc etc
- LH, FSH, Oxytocin, Prolactin
- GH, TSH, ACTH, MSH…
3
Q
What is the structure of the hypothalamus?
A
- bilateral symmetry
- forms walls, floor of 3rd ventricle
- 3rd ventricle contains cerebrospinal fluid
- lateral, supraoptic, paraventricular, arcuate, ventromedial, suprachiasmatic, medial preoptic and medial anterior hypothalamic nuclei
- brain originates embryologically as a tube of neural tissue
- floor of the tube is the thalamus
- hypothalamus below the thalamus
- complicated structure
- cavity in the middle of the hollow tube stays as the third ventricle – midline
- optic chiasm right at the front of the hypothalamus
4
Q
What are the interactions between the hypothalamus and the pituitary?
A
hypothalamic nuclei
- tracts of nerves that run from them
- parvocellular neurons (small cell bodies)
- neurons from arcuate nucleus that terminate on a capillary plexus
- another group in the preoptic area terminating on the capillary bed
- magnocellular neurons (large cell bodies)
- paraventricular nucleus
- terminals in posterior pituitary
- cell bodies not in posterior pituitary
- different sorts of functions
portal blood system
- supplied by arteries running into the hypthalamus
- beautiful capillary bed
- when the capillary outflow coalesces into a series of vessels that come down into the pituitary abd make another capillary bed
- carries neurosecretory neurons released by parvocellular neurons straight the anterior pituitary where they can have an action
- the HPA
pituitary gland
- neural and oral ectoderm origin
- ectodermal – anterior pituitary
- neural – posterior pituitary (cell terminals)
numerous interconnections with other brain areas
5
Q
What are some of the key nuclei?
A
- paraventricular nucleus
- preoptic area
- supraoptic nucleus
- ventromedial nucleus
- arcuate nucleus
- median eminence (bulge on the midline)
- capillary beds come together here in the start of the HPA
- anterior pituitary
- posterior pituitary
6
Q
What is the HPA?
A
hypothalamo-pituitary axis
7
Q
what is HPG?
A
hypothalamo-pituitary-gonadal axis
8
Q
What is the hypophysis?
A
pituitary
(pituitary ablation (removal) = hypophysectomy)
9
Q
What is pars distalis?
A
anterior pituitary
10
Q
What is the pars nervosa?
A
posterior pituitary
11
Q
What is the pars intermedia?
A
intermediate lobe
12
Q
What is the infundibulum?
A
pituitary stalk
13
Q
What are the anterior pituitary cells?
A
- Gonadotroph secretes LH and/or FSH
- Lactotroph secretes prolactin
14
Q
What are the magnocellular neurons?
A
- make oxytocin and vasopressin
- large cell bodies in paraventricular and supraoptic nuclei
- axons run down pituitary stalk
- terminate in posterior pituitary
- release oxytocin (OT) and VP
15
Q
What is oxytocin?
A
- uterine contractions
- mammary milk ejection
- maternal behaviour
- luteolysis: made in the CL
- neurohormone
- released from posterior pituitary
*
18
Q
How is GnRH secreted?
A
- In pulses
- pulse generator in hypothalamus sets frequency of pulses
- GnRH in portal blood is pulsatile
- LH secretion is also pulsatile and coincides with GnRH pulses
- pulse frequency varies with species/reprod
- ewe 1 pulse/2 hours
- Rhesus monkey 1 pulse / hour
- looks like GnRH pulses drive LH pulses
- pulse frequency isn’t constant
- use sheep because much easier to access sheep skull surgically
- pulsatile GnRH → LH and FSH release
- continuous GnRH → basal LH and FSH release
- pituitary GnRH receptors down regulated
- GnRH regulates its own receptor
- receptors internalised and can no longer respond
- GnRH pulse generator is a central regulator of reproductive activity
- Experimental model: Rhesus monkey
- ovariectomised
- hypothalamus lesioned;
- given GnRH by infusion
- LH and FSH go down when continuous GnRH, go up when pulsatile
20
Q
What is the neuroendocrine control of the testis?
A
- testes putting out testosterone and inhibin
- feedback on the hypothalamus and pituitary
- regulate GnRH pulses
- GnRH pulses control LH pulses
- if we take out the testes:
- no testosterone and inhibin produced by testes
- GnRH levels increase
- LH and FSH levels go up
- reduction of negative feedback
21
Q
Can DHT be converted to oestrogens?
A
- no
- T but not DHT can be converted to oestrogens
- T to DHT is a one way conversion
22
Q
What was seen in the HPG axis in a ram?
A
- castrated rams (wethers) + T, CHT, E2 or control
- all treatments: ↓ LH, ↓ FSH, ↓ pulse frequency
- hypothalamo-pituitary (HPD) disconnected wethers with GnRH pulses infused every 2 h
- all treatments: no effect on LH or FSH
- therefore both androgen and oestrogen receptors in the hypothalamus responsible for some of that feedback
- wethers: portal blood samples for GnRH ± testosterone
- effect of T:
- ↓ GnRH conc
- ↓ GnRH pulse frequency
- ↓ GnRH pulse amplitude
- effect of T:
23
Q
How are LH and FSH secreted in women?
A
- feedback control
- oestradiol and inhibin
- post menopausal
- release from oestradiol feedback
- pulse frequency changed
- LH and FSH levels reversed
- inhibin effect?
- if oestradiol increased (200% or more)
- +ve feedback occurs leading to LH, FSH surge
25
Q
What is the LH secretion pattern in menstrual cycle?
A
- LH pulsatility varies during the ovulatory cycle
- Pre-ovulation LH pulse frequency steady but LH levels rise
- early follicular phase: relatively small, frequenct LH pulses
- early luteal: progesterone high, oestradiol small, infrequenty but large pulses
