Pulsatile GnRH and the onset of puberty
Puberty starts when the hypothalamus increases its release of GnRH (gonadotropin-releasing hormone) in pulses, making the front part of the pituitary gland release FSH (follicle-stimulating hormone) and LH (luteinising hormone).
Remember
Puberty is started by increased pulses of GnRH from the hypothalamus, which stimulate the pituitary gland to release FSH and LH; a constant level of GnRH has the opposite effect, because the pituitary cells become desensitised (they stop responding).
During childhood, the GnRH pulse generator is held in check. This is the network of neurons in the hypothalamus that releases gonadotrophin-releasing hormone in pulses. Puberty starts when the generator is reactivated, so the hypothalamus again releases GnRH in pulses.
At the start of puberty the pulses come roughly every 1 to 3 hours during sleep, and the rise first appears at this time, which links to circadian rhythm. Each pulse reaches the anterior pituitary (the front part of the pituitary gland) through small portal blood vessels. There it binds to receptors on the surface membrane of the gonadotroph cells, the cells that make FSH and LH. Second messengers (chemical relays inside the cell) then make the cell let out FSH and LH.
FSH and LH are called gonadotropins because they act on the gonads (the testes or ovaries). The gonads then make sex steroids, such as testosterone and oestrogen, which produce the body changes of puberty. So the order is hypothalamus, then pituitary, then gonads.
The pulsatile pattern (short bursts) matters as well as the amount. A constant level of GnRH has the opposite effect: the pituitary cells become desensitised (they stop responding), so less FSH and LH is let out. This is why long-acting GnRH agonist drugs (drugs that mimic GnRH) are used to treat central precocious puberty (puberty that starts abnormally early).
Delayed puberty is puberty that starts later than expected for age. Low LH and FSH usually point upstream, to the hypothalamus or pituitary gland. High LH and FSH point to the gonads, because the lack of negative feedback drives the pituitary gland.
Key facts
- Source
- GnRH comes from nerve cells in the hypothalamus, which release it in pulses.
- Timing
- at the start of puberty the pulses come roughly every 1 to 3 hours during sleep, and the rise first appears at this time.
- Target
- GnRH acts on receptors in the cell membrane of the gonadotroph cells in the anterior pituitary, and second messengers then trigger release of FSH and LH.
- Sequence
- GnRH pulses come first, then LH and FSH from the anterior pituitary, then sex steroids from the gonads.
- Constant exposure
- sustained stimulation desensitises the receptors, so it suppresses rather than stimulates FSH and LH release.
- Feedback
- sex steroids from the gonads provide negative feedback on the hypothalamus and pituitary, but once menstrual cycles are established high oestrogen levels act as positive feedback and trigger a surge in LH that causes ovulation.
Exam traps
- Continuous high-level GnRH does not keep the pituitary stimulated, because constant stimulation desensitises the GnRH receptors and lowers FSH and LH output.
- Daytime pulses are not the trigger, because the rise in GnRH pulses at the start of puberty first appears during sleep.
- A surge of GnRH release triggered by high oestrogen does not start puberty, because that positive feedback produces the LH surge that causes ovulation once menstrual cycles are established.
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