The pulsatile GnRH secretion from the hypothalamus is essential for normal LH/FSH release. Continuous (non-pulsatile) administration of a GnRH agonist causes:

• A Downregulation of GnRH receptors on gonadotrophs, causing gonadotropin suppression ✓
• B Upregulation of GnRH receptors, amplifying LH/FSH release persistently
• C Preferential FSH elevation relative to LH due to different pulse-frequency sensitivity
• D Stimulation of inhibin B secretion from the testis, selectively suppressing FSH

Explanation

When GnRH is given as a continuous infusion or depot agonist, GnRH receptors on gonadotrophs become desensitised and downregulated through receptor internalisation and uncoupling from Gq signalling. This results in a paradoxical fall in LH and FSH (medical castration), exploited therapeutically in prostate cancer and endometriosis. The normal physiology relies on the pulse frequency of GnRH: high frequency favours LH over FSH, and lower frequency favours FSH — but this is irrelevant here since sustained exposure abolishes both. Options B–D are incorrect descriptions.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.