Postnatal Development of Kisspeptin Neurons in Mouse Hypothalamus; Sexual Dimorphism and Projections to Gonadotropin-Releasing Hormone Neurons

TLDR

Kisspeptin is critical for activating GnRH neurons to trigger puberty. The study examined postnatal development of kisspeptin neurons and their projections to GnRH neurons in mice. Three kisspeptin neuron populations were identified in the AVPV/PeN, dorsomedial hypothalamus, and arcuate nucleus using antisera, and dual immunofluorescence revealed age‑dependent appositions between kisspeptin fibers and GnRH neuron cell bodies. A marked female‑dominant 10‑fold increase in AVPV/PeN kisspeptin neurons was observed, with postnatal development beginning at P25 and reaching adult levels by puberty, while dorsomedial and arcuate populations showed no such pattern; these periventricular neurons likely provide the kisspeptin input to GnRH neurons.

Abstract

The neuropeptide kisspeptin has recently been implicated as having a critical role in the activation of the GnRH neurons to bring about puberty. We examined here the postnatal development of kisspeptin neuronal populations and their projections to GnRH neurons in the mouse. Three populations of kisspeptin neurons located in the 1) anteroventral periventricular nucleus (AVPV) and the preoptic periventricular nucleus (PeN), 2) dorsomedial hypothalamus, and 3) arcuate nucleus were identified using an antisera raised against mouse kisspeptin-10. A marked 10-fold (P < 0.01), female-dominant sex difference in the numbers of kisspeptin neurons existed in the AVPV/PeN but not elsewhere. Kisspeptin neurons in the AVPV/PeN of both sexes displayed a similar pattern of postnatal development with no cells detected at postnatal day (P) 10, followed by increases from P25 to reach adult levels by puberty onset (P < 0.01; P31 females and P45 males). This pattern was not found in the dorsomedial hypothalamus or arcuate nucleus. Dual immunofluorescence experiments demonstrated close appositions between kisspeptin fibers and GnRH neuron cell bodies that were first apparent at P25 and increased across postnatal development in both sexes. These studies demonstrate kisspeptin peptide expression in the mouse hypothalamus and reveal the postnatal development of a sexually dimorphic continuum of kisspeptin neurons within the AVPV and PeN. This periventricular population of kisspeptin neurons reaches adult-like proportions at the time of puberty onset and is the likely source of the kisspeptin inputs to GnRH neurons.