Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Dissecting the role of specific brain circuits in polycystic ovary syndrome (PCOS) (#149)

Rebecca Campbell 1
  1. University of Otago, Dunedin, New Zealand

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the leading cause of anovulatory infertility. Characterised by hyperandrogenism, menstrual dysfunction and polycystic ovaries, PCOS is commonly considered an ovarian disease.  However, the brain is now a prime candidate in both the ontogeny and pathology of PCOS, as steroid hormone negative feedback to the hypothalamic-pituitary axis is frequently impaired in PCOS. Our work, in a prenatally androgenized (PNA) mouse model of the syndrome, has identified changes within the gonadotropin-releasing hormone (GnRH) neuronal network that controls pituitary gonadotropin secretion and ultimately fertility. Specifically, GABA neurons originating within the arcuate nucleus (ARN) of the hypothalamus send significantly more inputs to the GnRH neurons in a PCOS-like state.  ARN GABA neurons are steroid hormone sensitive but are less sensitive to progesterone in PNA animals, suggesting that these circuit changes may reflect and mediate the neuroendocrine pathology of PCOS. Recently, we have investigated the functional impact of selective ARN GABA neuron activation with cre-dependent optogenetics and identified that specific activation ARN GABA neurons projecting to GnRH neurons leads to a dramatic and long lasting increase in lutienising hormone secretion. Together, these data suggest that ARN GABA neurons may be responsible for driving the hyperactive GnRH/ LH system and associated downstream consequences of PCOS.