Activation of the hypothalamic-pituitary-gonadal axis at puberty requires reactivation of pulsatile GnRH secretion. Which upstream signal is considered the central gatekeeper initiating this pubertal reactivation?

• A Melatonin withdrawal acting directly on GnRH neurons
• B Kisspeptin acting on GPR54 receptors on GnRH neurons ✓
• C Leptin binding to receptors on pituitary gonadotrophs
• D Direct adrenal androgen stimulation of hypothalamic GnRH cells

Explanation

Puberty is initiated when kisspeptin signalling onto GPR54 (kiss1r) receptors on GnRH neurons increases, driving pulsatile GnRH release and awakening the dormant axis. Mutations in KISS1 or GPR54 cause hypogonadotropic hypogonadism with absent puberty, proving causality. Leptin is permissive, signalling energy sufficiency to kisspeptin neurons rather than acting on the pituitary, so C misplaces both site and pathway. Melatonin influences pubertal timing in some contexts but is not the gatekeeper, and adrenal androgens drive adrenarche, not gonadarche.

Reference: Williams Textbook of Endocrinology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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