Hypothalamic-pituitary Gonadal Axis

Question 1

what does the HPGA influence in females

Answer 1

folliculogenesis and ovulation

Question 2

what is folliculogenesis

Answer 2

the progression of a number of small primordial follicles into large preovulatory follicles that enter the menstrual cycle

Question 3

what does the HPGA influence in men

Answer 3

spermatogenesis

Question 4

what is the HPGA

Answer 4

hypothalamus -> GnRH -> acts on receptors on the ant pituitary -> inc synthesis and relase of FSH and LH
FSH and LH -> act on receptors in gonads to increase gonadal steroids and peptide hormones

Question 5

what are the gonadal hormones

Answer 5

• oestrogen which is made in males and females
• progesterone which is only female
• androgens only in males

Question 6

how is the HPGA regulated

Answer 6

if conc is high in BS Gonadal hormones act on hypothalamus and ant. pituitary themselves to turn down release
oestrogen may positively feed back in female menstrual cycle (LH and oestrogen surge)

Question 7

what does the hypothalamus release

Answer 7

GnRH

Kisspeptin

Question 8

what does the ant. pituitary release

Answer 8

FSH

LH

Question 9

what do the gonads release

Answer 9

Female - Oestrodiol (E2) &Progesterone (P4)

Male - testosterone (also inhibin and activin, peptide hormones)

Question 10

what is the broad function of gonadal steroids

Answer 10

co-ordinate gonadal function for viable gamete production (in males bc new sperm constantly produced)
growth and development (males and females)

Question 11

what is the role of kisspeptin

Answer 11

involved in controlling GnRH release.

Question 12

what stimulates the release of GnRH from hypothalamus

Answer 12

Neural input to specialised hypothalamic neurones

Question 13

where are hypothalamic hormones released

Answer 13

into the median eminence which flow into the portal circulation.
to the ant pituitary

Question 14

what is GnRH

Answer 14

peptide hormone

only 10 AA

Question 15

where is GnRH sythesised

Answer 15

synthesised and secreted from specialised GnRH neurones of the hypothalamus.

Question 16

in what manner must GnRH be released

Answer 16

in a pulsatile manner.

if released in a continuous manner it stops working

Question 17

what allows pulsatile release of GnRH

Answer 17

there is a pulse generator in the hypothalamus which cause their release.

Question 18

where does GnRH exert its action

Answer 18

the GnRH receptor (a GPCR) on gonadotroph cells of the anterior pituitary

Question 19

what is the effect of GnRH

Answer 19

increasing gene transcription of the alpha and beta subunits of LH and FSH

Question 20

in what manner are LH and FSH released from ant pituitary

Answer 20

assembled and packaged into vesicles and released in a pulsatile manner corresponding to pulses of GnRH

Question 21

what determines the frequency of pulses

Answer 21

pulse every 30-120 minutes
men - about every hr
women - frequency depends on the part of the menstrual cycle.

Question 22

how does frequency of GnRH pulsing affect pituitary release

Answer 22

• Slow frequency pulses of GnRH release favours FSH release

- Rapid frequency pulsing of GnRH favours LH

Question 23

what is synthetic GnRH used for

Answer 23

Exactly same structure as our normal body GnRH

generally used to stimulate the HPG axis e.g. in delayed puberty

Question 24

what is GnRH analogue used for

Answer 24

Modified versions of GnRH, they have a modified peptide structure and used to down regulate HPG axis

Question 25

How do GnRH analogues regulate the HPGA

Answer 25

result in a loss of pulsatility and there can be agonist analogues or antagonists analogues each work in different ways

Question 26

what is the mechanism of action of normal and synthetic GnRH

Answer 26

1 - GnRH binds in ant pituitary 2 - activation of intracellular signalling and stimulation of LH and FSH synthesis and secretion 3 - GnRH dissociates from its receptor .'. signalling stops 4 - receptor ready to respond to next GnRH pulse

Question 27

what is the mechanism of action of GnRH agonist analogues

Answer 27

1 - agonist binds in ant pituitary (has affinity and efficacy) 2 - activation of intracellular signalling 3 - stimulation of GnRH synthesis and secretion 4 - uncoupling of GnRH from receptor (doesn't dissociate, remains bound) 5 - over time GnRH becomes unresponsive to GnRH so get decreased release of gonadotrophin

Question 28

what is the mechanism of action of GnRH antagonist analogues

Answer 28

1 - agonist binds in ant pituitary 2 - no efficacy .'. receptor is blocked 3 - no downstream effects 4 - downregulation of gonadotrophin (as receiving no stimulation)

Question 29

What are clinical uses of GnRH analogues

Answer 29

- Ovulation induction and IVF - Prostate cancer (if a cancer is hormone responsive, you may want to shut down gonadal steroid production) - uterine fibroids - endometriosis - PCOS

Question 30

what is the structure of the gonadotrophs

Answer 30

heterodimeric peptides are all glycosylated and have N-linked sidechains - common a-subunit in all gonad hormones - b-subunit is specific to each hormone and confers biological specificity

Question 31

what are the gonadotropin hormones

Answer 31

LH, FSH and hCG

Question 32

in what manner are gonadotrophs released

Answer 32

in a pulsatile manner (following from GnRH pulse release. | do not require pulse release for bio activity

Question 33

how does nutrition affect HPGA

Answer 33

in a underweight person there is a loss of amplitude in the pulses - diminished LH and FSH - down regulation of HPG axis - decreased folliculogenesis.

Question 34

what is the function of LH in males

Answer 34

• Acts on testis where it causes stimulation of Leydig cells to increase androgen (testosterone) synthesis

Question 35

what is the function of LH in females

Answer 35

acts on ovary: - Increase theca cell androgen synthesis during follicular phase - essential for mediating ovulation - Stimulates progesterone production from corpus luteum

Question 36

what is the role of FSH in men

Answer 36

• Acts in the testis where it regulates Sertoli cell metabolism, Sertoli cells support spermatogenesis so this process is essential for spermatogenesis

Question 37

what is the role of FSH in females

Answer 37

acts in ovary: - Essential for causing follicular maturation - Essential for granulosa cells to synthesise oestrogen

Question 38

what do leydig cells do

Answer 38

Express LH receptors, which mediate androgen (testosterone) production

Question 39

what do sertoli cells do

Answer 39

Express FSH receptors, which mediate sertoli cell metabolism and spermatogenesis

Question 40

what do theca cells do

Answer 40

Part of follicles, express the LH receptors, when stimulated produce androgens, which travel to granulosa cells

Question 41

what do granulosa cells do

Answer 41

Part of follicles, express FSH receptors, under the action of FSH androgens are converted to oestrogens by aromatase

Question 42

what is the corpus luteum

Answer 42

The remnant of the follicle, contains LH receptors and FSH receptors, the former mediates release of progesterone