Investigating the NPY/AgRP/GABA to GnRH neuron circuit in prenatally androgenized PCOS-like mice

Marshall, C. J. , Prescott, M. and Campbell, R. E. (2020) Investigating the NPY/AgRP/GABA to GnRH neuron circuit in prenatally androgenized PCOS-like mice. Journal of the Endocrine Society, 4(11), bvaa129. (doi: 10.1210/jendso/bvaa129) (PMID:33094210) (PMCID:PMC7566551)

Abstract

Polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility, is associated with altered signaling within the hormone-sensitive neuronal network that regulates gonadotropin-releasing hormone (GnRH) neurons, leading to a pathological increase in GnRH secretion. Circuit remodeling is evident between GABAergic neurons in the arcuate nucleus (ARN) and GnRH neurons in a murine model of PCOS. One-third of ARN GABA neurons co-express neuropeptide Y (NPY), which has a known yet complex role in regulating GnRH neurons and reproductive function. Here, we investigated whether the NPY-expressing subpopulation (NPYARN) of ARN GABA neurons (GABAARN) is also affected in prenatally androgenized (PNA) PCOS-like NPYARN reporter mice [Agouti-related protein (AgRP)-Cre;τGFP]. PCOS-like mice and controls were generated by exposure to di-hydrotestosterone or vehicle (VEH) in late gestation. τGFP-expressing NPYARN neuron fiber appositions with GnRH neurons and gonadal steroid hormone receptor expression in τGFP-expressing NPYARN neurons were assessed using confocal microscopy. Although GnRH neurons received abundant close contacts from τGFP-expressing NPYARN neuron fibers, the number and density of putative inputs was not affected by prenatal androgen excess. NPYARN neurons did not co-express progesterone receptor or estrogen receptor α in either PNA or VEH mice. However, the proportion of NPYARN neurons co-expressing the androgen receptor was significantly elevated in PNA mice. Therefore, NPYARN neurons are not remodeled by prenatal androgen excess like the wider GABAARN population, indicating GABA-to-GnRH neuron circuit remodeling occurs in a presently unidentified non-NPY/AgRP population of GABAARN neurons. NPYARN neurons do, however, show independent changes in the form of elevated androgen sensitivity.

• Item Type: Articles
• Additional Information: Financial Support: New Zealand Health Research Council grants 15–097 and 18–671, Royal Society Marsden Fund grants 14–077 and 17–064.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Marshall, Dr Christopher
• Authors: Marshall, C. J., Prescott, M., and Campbell, R. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Journal of the Endocrine Society
• Publisher: Oxford University Press
• ISSN: 2472-1972
• ISSN (Online): 2472-1972
• Published Online: 31 August 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Journal of the Endocrine Society 4(11): bvaa129
• Publisher Policy: Reproduced under a Creative Commons License