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Repro > Hypothalamic-pituitary Gonadal Axis > Flashcards

Hypothalamic-pituitary Gonadal Axis Flashcards

1
Q

what does the HPGA influence in females

A

folliculogenesis and ovulation

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2
Q

what is folliculogenesis

A

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

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3
Q

what does the HPGA influence in men

A

spermatogenesis

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4
Q

what is the HPGA

A

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

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5
Q

what are the gonadal hormones

A
  • oestrogen which is made in males and females
  • progesterone which is only female
  • androgens only in males
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6
Q

how is the HPGA regulated

A

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)

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7
Q

what does the hypothalamus release

A

GnRH

Kisspeptin

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8
Q

what does the ant. pituitary release

A

FSH

LH

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9
Q

what do the gonads release

A

Female - Oestrodiol (E2) &Progesterone (P4)

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

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10
Q

what is the broad function of gonadal steroids

A

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

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11
Q

what is the role of kisspeptin

A

involved in controlling GnRH release.

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12
Q

what stimulates the release of GnRH from hypothalamus

A

Neural input to specialised hypothalamic neurones

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13
Q

where are hypothalamic hormones released

A

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

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14
Q

what is GnRH

A

peptide hormone

only 10 AA

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15
Q

where is GnRH sythesised

A

synthesised and secreted from specialised GnRH neurones of the hypothalamus.

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16
Q

in what manner must GnRH be released

A

in a pulsatile manner.

if released in a continuous manner it stops working

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17
Q

what allows pulsatile release of GnRH

A

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

18
Q

where does GnRH exert its action

A

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

19
Q

what is the effect of GnRH

A

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

20
Q

in what manner are LH and FSH released from ant pituitary

A

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

21
Q

what determines the frequency of pulses

A

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

22
Q

how does frequency of GnRH pulsing affect pituitary release

A
  • Slow frequency pulses of GnRH release favours FSH release

- Rapid frequency pulsing of GnRH favours LH

23
Q

what is synthetic GnRH used for

A

Exactly same structure as our normal body GnRH

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

24
Q

what is GnRH analogue used for

A

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

25
Q

How do GnRH analogues regulate the HPGA

A

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

26
Q

what is the mechanism of action of normal and synthetic GnRH

A

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

27
Q

what is the mechanism of action of GnRH agonist analogues

A

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

28
Q

what is the mechanism of action of GnRH antagonist analogues

A

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

29
Q

What are clinical uses of GnRH analogues

A
  • 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
30
Q

what is the structure of the gonadotrophs

A

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

31
Q

what are the gonadotropin hormones

A

LH, FSH and hCG

32
Q

in what manner are gonadotrophs released

A

in a pulsatile manner (following from GnRH pulse release.

do not require pulse release for bio activity

33
Q

how does nutrition affect HPGA

A

in a underweight person there is a loss of amplitude in the pulses

  • diminished LH and FSH
  • down regulation of HPG axis
  • decreased folliculogenesis.
34
Q

what is the function of LH in males

A

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

35
Q

what is the function of LH in females

A

acts on ovary:

  • Increase theca cell androgen synthesis during follicular phase
  • essential for mediating ovulation
  • Stimulates progesterone production from corpus luteum
36
Q

what is the role of FSH in men

A

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

37
Q

what is the role of FSH in females

A

acts in ovary:

  • Essential for causing follicular maturation
  • Essential for granulosa cells to synthesise oestrogen
38
Q

what do leydig cells do

A

Express LH receptors, which mediate androgen (testosterone) production

39
Q

what do sertoli cells do

A

Express FSH receptors, which mediate sertoli cell metabolism and spermatogenesis

40
Q

what do theca cells do

A

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

41
Q

what do granulosa cells do

A

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

42
Q

what is the corpus luteum

A

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

Repro (13 decks)

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