Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a distressing condition and a prevalent cause of anovulatory infertility in individuals of reproductive age. Although PCOS is characterized by ovary dysfunction, growing evidence suggests that the brain plays a crucial role in the development and pathophysiology of the syndrome. In PCOS patients, there is an impairment in gonadal steroid hormone negative feedback to the hypothalamus, which contains the gonadotropin-releasing hormone (GnRH) neuronal network that governs fertility. This leads to an increase in GnRH and pituitary luteinizing hormone (LH) pulsatile release, which, in turn, acts on the ovary to induce ovarian dysfunction and hyperandrogenism. Androgen excess may then act back on the brain to further promote GnRH secretion, resulting in a vicious cycle that continually promotes androgen secretion and reproductive symptoms. The location and mechanistic changes that underlie impaired steroid hormone feedback remain unknown due to the challenges of studying the human hypothalamus at the cellular level. However, in recent years, animal models generated using exposure to excess androgens during critical developmental periods have significantly advanced our understanding of the brain’s role in PCOS. In this talk, I will discuss recent results that identify key neural circuits involved in controlling GnRH release, as well as evidence showing that disruptions in these circuits play a crucial role in the pathogenesis of PCOS symptoms in animal models. In particular, this talk will emphasize new evidence regarding the role of cells in the arcuate nucleus of the hypothalamus that express the neuropeptide kisspeptin, which constitutes the GnRH pulse generator, in the syndrome’s pathogenesis. Overall, this talk will highlight that identifying and understanding central defects will be vital for establishing effective treatments for PCOS.