A Population of Kisspeptin/Neurokinin B Neurons in the Arcuate Nucleus May Be the Central Target of the Male Effect Phenomenon in Goats

Kohei Sakamoto,Tomomi Tanaka,Yoshihiro Wakabayashi,Yukari Takeuchi,Hiroaki Okamura,Yuji Mori,Takashi Yamamura,Hubert Vaudry

doi:10.1371/journal.pone.0081017

Abstract

Exposure of females to a male pheromone accelerates pulsatile gonadotropin-releasing hormone (GnRH) secretion in goats. Recent evidence has suggested that neurons in the arcuate nucleus (ARC) containing kisspeptin and neurokinin B (NKB) play a pivotal role in the control of GnRH secretion. Therefore, we hypothesized that these neurons may be the central target of the male pheromone. To test this hypothesis, we examined whether NKB signaling is involved in the pheromone action, and whether ARC kisspeptin/NKB neurons receive input from the medial nucleus of the amygdala (MeA)—the nucleus suggested to relay pheromone signals. Ovariectomized goats were implanted with a recording electrode aimed at a population of ARC kisspeptin/NKB neurons, and GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA) volleys, was measured. Pheromone exposure induced an MUA volley and luteinizing hormone (LH) pulse in control animals, whereas the MUA and LH responses to the pheromone were completely suppressed by the treatment with an NKB receptor antagonist. These results indicate that NKB signaling is a prerequisite for pheromone action. In ovariectomized goats, an anterograde tracer was injected into the MeA, and possible connections between the MeA and ARC kisspeptin/NKB neurons were examined. Histochemical observations demonstrated that a subset of ARC kisspeptin/NKB neurons receive efferent projections from the MeA. These results suggest that the male pheromone signal is conveyed via the MeA to ARC kisspeptin neurons, wherein the signal stimulates GnRH pulse generator activity through an NKB signaling-mediated mechanism in goats.

Highlights

In sheep and goats, the exposure of seasonally anestrous females to sexually mature males accelerates reproductive activity and subsequently induces out-of-season ovulation [1,2,3,4,5], a phenomenon called the “male effect.” The male–female interaction consists of several factors, including olfactory, visual, auditory, and tactile/behavioral cues [4,5]
We demonstrated in goats that pheromone action on gonadotropinreleasing hormone (GnRH) pulse generator activity depends on entirely neurokinin B (NKB) signaling, and arcuate nucleus (ARC) kisspeptin neurons receive projections from the medial nucleus of the amygdala (MeA)
The MeA is considered to be a key neural substrate that relays pheromone signals to target nuclei in the hypothalamus [41,42,43,52]. Considering these findings, the present results strongly suggest that the male pheromone signal is transmitted to, and processed in, a subset of ARC kisspeptin/NKB neurons, triggering pulsatile GnRH/luteinizing hormone (LH) secretion

Summary

Introduction

The exposure of seasonally anestrous females to sexually mature males accelerates reproductive activity and subsequently induces out-of-season ovulation [1,2,3,4,5], a phenomenon called the “male effect.” The male–female interaction consists of several factors, including olfactory, visual, auditory, and tactile/behavioral cues [4,5]. The male effect was initially identified as the phenomenon in anestrous females of seasonal breeders [1,2,3,4,5], our previous studies have shown that the induction of the MUA volley by the male pheromone can be observed independent of the season in ovariectomized (OVX) Shiba goats [10,19,20,21,22] In this experimental representation of the male effect, timing of pheromone exposure is critical [10,19]. The neural identity for the central target of the male pheromone remains unknown

Methods

Results

Conclusion