Kisspeptin Restores Pulsatile LH Secretion in Patients with Neurokinin B Signaling Deficiencies

Pulsatile gonadotropin-releasing hormone (GnRH) is crucial to normal reproductive function and abnormalities in pulse frequency give rise to reproductive dysfunction. Kisspeptin and neurokinin B (NKB), neuropeptides secreted by the same neuronal population in the ventral hypothalamus, have emerged recently as critical central regulators of GnRH and thus gonadotropin secretion. Patients with mutations resulting in loss of signaling by either of these neuroendocrine peptides fail to advance through puberty but the mechanisms mediating this remain unresolved. We report here that continuous kisspeptin infusion restores gonadotropin pulsatility in patients with loss-of-function mutations in NKB ( TAC3 ) or its receptor ( TAC3R ), indicating that kisspeptin on Received: October 4, 2011 Accepted after revision: January 5, 2012 Published online: February 24, 2012 Robert P. Millar Mammal Research Institute, University of Pretoria Pretoria 0028 (South Africa) Tel. +27 420 3776 E-Mail robertpetermillar @ gmail.com © 2012 S. Karger AG, Basel 0028–3835/13/0972–0193$38.00/0 www.karger.com/nen Th is is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (www.karger.com/OA-license-WT), applicable to the online version of the article only. Distribution for noncommercial purposes only. D ow nl oa de d by : 94 .1 74 .2 02 .1 47 5 /3 1/ 20 13 6 :2 4: 01 P M