Evidence That Agouti-Related Peptide May Directly Regulate Kisspeptin Neurons in Male Sheep.

Christina M Merkley,Jeffrey R Sommer,Casey C Nestor,Sydney L Shuping

doi:10.3390/metabo11030138

Christina M Merkley, Jeffrey R Sommer + Show 2 more

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https://doi.org/10.3390/metabo11030138

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Journal: Metabolites	Publication Date: Feb 26, 2021
Citations: 10	License type: CC BY 4.0

Affiliation: North Carolina State University

Abstract

Agouti-related peptide (AgRP) neurons, which relay information from peripheral metabolic signals, may constitute a key central regulator of reproduction. Given that AgRP inhibits luteinizing hormone (LH) secretion and that nutritional suppression of LH elicits an increase in AgRP while suppressing kisspeptin expression in the arcuate nucleus (ARC) of the hypothalamus, we sought to examine the degree to which AgRP could directly regulate ARC kisspeptin neurons. Hypothalamic tissue was collected from four castrated male sheep (10 months of age) and processed for the detection of protein (AgRP input to kisspeptin neurons) using immunohistochemistry and mRNA for melanocortin 3 and 4 receptors (MC3R; MC4R) in kisspeptin neurons using RNAscope. Immunohistochemical analysis revealed that the majority of ARC kisspeptin neurons are contacted by presumptive AgRP terminals. RNAscope analysis revealed that nearly two thirds of the ARC kisspeptin neurons express mRNA for MC3R, while a small percentage (<10%) colocalize MC4R. Taken together, this data provides neuroanatomical evidence for a direct link between orexigenic AgRP neurons and reproductively critical kisspeptin neurons in the sheep, and builds upon our current understanding of the central link between energy balance and reproduction.

Highlights

Agouti-related peptide (AgRP) neurons and reproductively critical kisspeptin neurons in the sheep, and builds upon our current understanding of the central link between energy balance and reproduction
We examine the degree to which arcuate nucleus (ARC) kisspeptin perikarya are innervated by presumptive AgRP terminals using dual-label immunofluorescence, and utilizing a relatively new fluorescent in situ hybridization technique, RNAscope, we characterize the degree to which arcuate kisspeptin neurons colocalize melanocortin 3 and receptors (MC3R) and MC4R
AgRP Inputs to Kisspeptin Cells In ARC tissue from 10 month old castrated male sheep, AgRP-immunoreactive terminals were observed in frequent apposition to kisspeptin cell bodies and fibers (Figure 1)

Summary

Introduction

AgRP neurons and reproductively critical kisspeptin neurons in the sheep, and builds upon our current understanding of the central link between energy balance and reproduction. This, at least in part, occurs via central integration of metabolic signals given that negative energy balance inhibits gonadotropin-releasing hormone (GnRH), and subsequently luteinizing hormone (LH), release [1,2,3]. GnRH neurons in order to suppress GnRH/LH release during a negative energy state. One such stimulatory afferent is the neuropeptide kisspeptin, which has perikarya located primarily in two areas of the ventral forebrain, the anterior ventral periventricular area (AVPV; rodents)/preoptic area (POA; non-rodents) and the arcuate nucleus (ARC) of the hypothalamus [7,8,9]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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