Discovery of microglia gonadotropin‑releasing hormone receptor and its potential role in polycystic ovarian syndrome

Mol Med Rep. 2023 Apr;27(4):77. doi: 10.3892/mmr.2023.12964. Epub 2023 Feb 17.

Abstract

Hypothalamic inflammation is a pathophysiological basis of polycystic ovarian syndrome (PCOS), while overactivated and/or excess M1 polarized microglia are considered to be the main reason for the occurrence of hypothalamic inflammation. Therefore, in vitro and in vivo experiments were performed to assess the relationships between microglia‑mediated inflammatory reactions and endocrine functions in the PCOS hypothalamus. The expression of gonadotropin‑releasing hormone (GnRH) receptor (GnRHR) was demonstrated in hypothalamic microglia, and it was found that low concentration, GnRH agonist, leuprolide acetate accelerated the expression of M2 polarization marker CD206, while high concentration leuprolide acetate increased the expression of M1 polarization marker CD86 in vitro. Furthermore, aerobic exercise not only reduced the levels of serum testosterone, luteinizing hormone and GnRH and the amount of overactivated microglia, but also increased the number of M2 microglia in the hypothalamus of letrozole‑induced PCOS rats. In combination, these results not only demonstrated the expression of GnRHR in hypothalamic microglia, but also demonstrated that GnRH can induce microglial polarization, while aerobic exercise may improve the microglia‑mediated inflammatory reaction by reducing the expression of GnRHR in the hypothalamic microglia of PCOS rats.

Keywords: aerobic exercise; gonadotropin‑releasing hormone receptor; hypothalamic inflammation; microglia; polycystic ovarian syndrome.

MeSH terms

  • Animals
  • Female
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Leuprolide / pharmacology
  • Microglia / metabolism
  • Polycystic Ovary Syndrome* / metabolism
  • Rats
  • Receptors, LHRH / genetics

Substances

  • Receptors, LHRH
  • Leuprolide
  • Gonadotropin-Releasing Hormone

Grants and funding

This research was funded by the Key Projects of Scientific and Technological Innovation in Fujian Province (grant nos. 2021G02003, 2022G023 and 2022G028), Special Funds of the Central Government Guiding Local Science and Technology Development (grant no. 2020L3008), Fujian Provincial Natural Science Foundation (grant nos. 2019R1011-3, 2020J01176 and 2022J01172), Scientific Research Talent Project of Fujian Provincial Health Commission (grant no. 2018-ZQN-20), and the Innovation and Entrepreneurship Project of Fujian Normal University (grant nos. I202003009 and I202102008).