GnRH Agonist
A synthetic peptide that activates the gonadotropin-releasing hormone receptor. When administered continuously, GnRH agonists paradoxically suppress reproductive hormone production through receptor downregulation after an initial stimulatory phase. Approved examples include goserelin, leuprolide, triptorelin, histrelin, and nafarelin.
Technical Context
GnRH agonists exploit the pulsatility-dependence of the GnRH receptor. Natural GnRH is released in pulses (approximately every 60-90 minutes) — this pulsatile pattern is essential for maintaining normal LH and FSH secretion. Continuous GnRH exposure (from depot or implant formulations) initially stimulates gonadotropin release (flare phase, 1-2 weeks), then causes receptor desensitisation, downregulation (reduced receptor number), and uncoupling from intracellular signalling pathways. The net result is profound suppression of LH, FSH, and downstream sex steroids (testosterone, oestrogen) to castrate or postmenopausal levels. This paradoxical use of agonists to achieve suppression is the pharmacological basis for treating hormone-sensitive prostate cancer, endometriosis, precocious puberty, and for pituitary suppression in fertility protocols.