HPG axis

Question 1

Hypothalamus to pituitary gland connection

Answer 1

via infundibulum (arcuate nucleus)
to adenohypophysis (anterior pituitary gonadotroph cells)

Question 2

Kisspeptin (KISS1)

Answer 2

Controls synthesis and secretion of GnRH in GnRH neurons.
Upstream of GnRH.
Hypothalamic expression - ARC and AVPV (species dependent).
Expression regulated by gonadal steroids - Regions express ER, PR.

Question 3

Kisspeptin receptor

Answer 3

Expressed on GnRH neurones

The Kisspeptin/KISS1R system is a component trigger of puberty.

Inactivating mutations of KISS1R and Kisspeptin = failure to undergo spontaneous puberty.

Activating KISS1R mutations can lead to precocious puberty.

Question 4

How does KISS1 regulate GnRH secretion

Answer 4

Hypothalamic explants from mice shown kisspeptin administration stimulates GnRH synthesis and secretion.

Kisspeptin neurons send projections to GnRH neurons, and binding to KISS1R expressed on GnRH neurons.

A bolus of Kisspeptin correlates with a peak of LH secretion.

Sexual dimorphic responses - cyclical differences.

Question 5

GnRH

Answer 5

Synthesised and secreted from specialised neurons of hypothalamus- GnRH neurons.

Secreted in a pulsatile fashion - pulse generator orchestrated.

Stimulates the synthesis and secretion of pituitary gonadotrophin hormones - LH and FSH.

Question 6

GnRH structure

Answer 6

Refer to lec slide

made of amino acids
Protein, signal peptide, GnRH, GAP

Question 7

GnRH pulsatility

Answer 7

GnRH is secreted in pulses from hypothalamus every 30-120min

A GnRH pulse stimulates a pulse of LH and FSH secretion from the pituitary

Pulsatile GnRH secretion is vital for stimulation of synthesis and secretion of LH/FSH

Slow frequency pulse favours FSHb transcription and FSH release, rapid pulse frequency favours LHb transcription and LH release

Continuous release results in cessation of response

Question 8

What is the mode of GnRH action

Answer 8

GnRH bind to GnRH receptor
Signal transduction
Gonadotrophin gene expression, synthesis and excretion

Question 9

Gonadotrophin hormone properties

Answer 9

Includes LH, FSH and hcG
They are glycoprotein hormones, are heterodimeric and secreted in pulsatile fashion

they all have a common alpha unit
Beta unit separate in LH and FSH giving it different properties

Question 10

Structure of gonadotrophin receptors

Answer 10

Extra cellular, transmembrane, intracellular

Question 11

Function of FSH

Answer 11

In testis: Sertoli cell metabolism

In ovaries: Follicular maturation, granulosa cell oestrogen synthesis

Question 12

Function of LH

Answer 12

Testis: Stimulation of leydig cell androgen synthesis

Ovary: theca cell androgen synthesis, ovulation, progesterone production of corpus luteum

This supports germ cell growth, maturation and development to enable it to be suitable for maturation

Question 13

Steroid hormone examples

Answer 13

Progesterone
Oestrogens
Oestradiol and also oestrone
Androgens
Androstenedione, testosterone, dihydrotestosterone

Question 14

Male gonadal steroid production

Answer 14

Leydig cells
LHR expression Androstenedione, DHEA, Testosterone production

Sertoli cells
FSHR expression Sertoli cell metabolism
Testosterone dihydrotestosterone

Question 15

Female gonadal steroid production

Answer 15

Corpus luteum
LHR (and FSHR) expression
Progesterone (and oestrogens)

1. Theca cells
   LHR expression
   Testosterone and Androstenedione
2. Granulosa cells
   FSHR expression Oestradiol and Oestrone

Question 16

Inhibin

Answer 16

Peptide hormones

Heterodimers

2 isoforms of inhibin: A and B.

Inhibin = gonadal, inhibits FSH secretion via direct negative feedback to anterior pituitary.

Males: Inhibin B

Females: cyclical dependent