Gonadotrophin-releasing hormone pulse generator (arcuate nucleus)
Hypothalamus · GnRH Kisspeptin Pulsatile
KNDy (kisspeptin, neurokinin B, dynorphin) neurones of the arcuate nucleus pace GnRH into the portal blood roughly every 60-90 minutes. The frequency, not the amount, decides whether LH or FSH dominates.
Detail
- Pulse code
- Fast pulses favour LH-beta transcription, slow pulses favour FSH-beta; continuous exposure desensitises the gonadotroph
- Therapeutic use
- Continuous GnRH agonist (goserelin, leuprorelin) gives an initial flare then medical castration in prostate cancer and endometriosis; pulsatile GnRH by pump restores fertility in hypothalamic disease
- Restrained by
- Prolactin, low energy availability and leptin, opioids, glucocorticoids; progesterone slows the pulse
When it goes wrong
Kallmann syndrome — failed migration of GnRH neurones with the olfactory placode
Hypogonadotrophic hypogonadism with anosmia: absent puberty, low LH, FSH and testosterone; gonadotrophins or pulsatile GnRH are needed for fertility
Functional hypothalamic amenorrhoea from low body weight, heavy training or stress
Slowed pulses give low LH and FSH with low oestradiol: secondary amenorrhoea, negative pregnancy test, normal prolactin and low bone density
GnRH agonist started for metastatic prostate cancer without antiandrogen cover
Testosterone flare in the first fortnight worsening bone pain or causing spinal cord compression
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