Testosterone-GnRH Frequency and the Evolution of PCOS in Adolescence
University of Virginia
PI: C. R. McCartney
Our primary goal is to understand the ontogeny of PCOS across pubertal development, especially with regard to abnormal gonadotropin-releasing hormone (GnRH) and gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) secretion. We will address two key gaps in knowledge: (1) How do the neuroendocrine abnormalities of PCOS (e.g., rapid GnRH pulse frequency and excessive LH secretion) develop during puberty? (2) Why does HA begin and progress in girls who go on to develop PCOS?
The proposed project involves clinical research studies designed to elucidate the role of P4 in directing daynight differences of GnRH pulse frequency during puberty in normal girls (Aim la); the role of testosterone (and HA) in modifying day-night regulation of GnRH pulse frequency (Aims lb and 1c); the role of HA in disrupting sex steroid positive feedback (LH surge generation) in late pubertal girls (Aim 2); and the sources and determinants of HA in some pubertal girls with obesity (Aim 3). These studies will synergize with the basic studies of Projects II and III to help elucidate the pubertal ontogeny of PCOS, all with a view to developing rational preventive strategies.