Pulsatile GnRH secretion at 90-minute intervals drives normal LH secretion. In a GnRH analogue protocol for IVF, continuous GnRH agonist administration is used for pituitary down-regulation. What is the primary mechanism of this paradoxical suppression?

• A Continuous receptor activation leads to GnRH receptor down-regulation and uncoupling from intracellular signalling (desensitisation), abolishing LH/FSH secretion ✓
• B Sustained GnRH activates hypothalamic opioid neurons that release beta-endorphin, inhibiting GnRH itself via an ultrashort feedback loop
• C Long-acting GnRH agonists bind androgen receptors in the pituitary, directly suppressing gonadotroph function
• D High-dose continuous GnRH stimulates inhibin B secretion from the ovary, which then feeds back to suppress gonadotrophs

Explanation

GnRH requires pulsatile delivery to maintain normal LH/FSH secretion because continuous stimulation induces receptor internalisation, down-regulation, and uncoupling of GnRH receptors from Gq-PLC signalling—a process called desensitisation or pituitary down-regulation. This is exploited in IVF protocols to prevent a premature LH surge. The beta-endorphin mechanism modulates pulse frequency rather than causing complete shut-down. GnRH agonists have no androgen receptor activity, and inhibin feedback modulates FSH selectively rather than the complete gonadotrophin suppression seen clinically.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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