Kisspeptin (Kiss1) neurons in the hypothalamus are critical regulators of the reproductive axis. In pubertal onset, the primary change in kisspeptin signaling is:

• A Reduction in kisspeptin sensitivity to estrogen negative feedback, allowing increased GnRH pulsatility ✓
• B Increased inhibition of kisspeptin neurons by gamma-aminobutyric acid (GABA)
• C De novo synthesis of GnRH receptors on pituitary gonadotrophs for the first time
• D Shift from leptin-driven to gonadal steroid-driven kisspeptin release

Explanation

Prepubertal restraint of the HPG axis is maintained largely by hypersensitivity of kisspeptin/GnRH neurons to gonadal steroid negative feedback, keeping GnRH pulses very low. Puberty is initiated when this negative feedback sensitivity decreases (possibly due to changes in epigenetic regulation of genes including MKRN3 and DLK1 that silence kisspeptin neurons), allowing kisspeptin pulse amplitude and frequency to increase, driving GnRH-LH/FSH pulsatility and ultimately gonadal maturation. Leptin serves as a permissive metabolic signal for puberty but the key change is reduced sensitivity to negative feedback.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.