0: Understanding neural circuit dysfunction in polycystic ovary syndrome (PCOS)

Approximately one in five women worldwide suffer from polycystic ovary
syndrome (PCOS), a condition typified by problems with fertility, high
androgen levels, and altered metabolism. Accruing clinical and
biomedical evidence indicates that over-activity of the hypothalamic
gonadotropin-releasing hormone (GnRH) pulse generator has a major
role in generating the subfertility of women with PCOS. The GnRH pulse
generator is responsible for driving the pulsatile release of reproductive
hormones in the general circulation that control ovarian function. Recent
studies have revealed that a population of kisspeptin neurons located in
the arcuate nucleus (ARN) of the hypothalamus is the long-sought after
"GnRH pulse generator". We aim to characterise the properties and
activity of the ARN kisspeptin neurons in a mouse model of PCOS, and
then explore the mechanism(s) behind the abnormal activity of the GnRH
pulse generator. This project will provide insight into the molecular
aetiology of disordered pulsatile hormone secretion in PCOS and
potentially, lay the foundations for opening up new therapeutic
opportunities in the clinic.