Hypothalamic-pituitary-gonadal axis regulation
Core concept
- GnRH pulse frequency is the control variable - not GnRH concentration
- Kisspeptin (KISS1/KISS1R) neurons in the arcuate nucleus are the gatekeeper; neurokinin B and dynorphin (KNDy neurons) set the pulse generator
- GnRH pulses every 60-120 min from the hypothalamus -> portal system -> gonadotrophs
- *Continuous GnRH DOWNREGULATES the receptor and suppresses LH/FSH* - the basis of GnRH agonist therapy
- Frequency codes for which gonadotrophin
- Fast pulses (~1/h) -> LH; slow pulses (~1/3 h) -> FSH
- Feedback
- Testosterone/oestradiol -> negative feedback on GnRH and LH
- Inhibin B (Sertoli/granulosa) -> selective negative feedback on FSH
- *The one positive feedback loop in endocrinology: sustained high oestradiol >~700-750 pmol/L for >36-48 h switches feedback to positive -> the LH surge -> ovulation*
- Puberty - reactivation of the pulse generator after childhood quiescence
- inc amplitude and frequency of GnRH pulses, initially nocturnal (sleep-entrained)
- Permissive signals: leptin (adequate fat mass), MKRN3 loss of inhibition, kisspeptin
3 more sections, plus exam facts
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