McCartney, Christopher R.
Professor, Medicine: Endocrinology and Metabolism
- MS, Health Evaluation Sciences, University of Virginia
- MD, , University of Mississippi
- Residency, Internal Medicine, University of Mississippi
- Clinical Fellowship, Endocrinology & Metabolism, University of Virginia
- Research Fellowship, , University of Virginia
UVA Division of Endocrinology & Metabolism
PO Box 801406
Charlottesville, VA 22908
Reproductive neuroendocrinology and polycystic ovary syndrome.
The long-term goal of our clinical (patient-oriented) research group is to understand the cause(s) of abnormal gonadotropin releasing hormone (GnRH) pulses and abnormal gonadotropin secretion in adolescent and adult polycystic ovary syndrome (PCOS). PCOS affects 6-8% of women and is marked by excess testosterone, irregular menses, and sub- or infertility. The cause(s) of PCOS is (are) unclear, but persistently rapid GnRH pulses contribute to high luteinizing hormone (LH) and diminished follicle-stimulating hormone (FSH) secretion, which in turn contribute to androgen excess and irregular ovulation. This defect is in part related to excess testosterone, which interferes with the ability of progesterone to reduce GnRH pulse frequency. Similar abnormalities of GnRH pulses and gonadotropin secretion are observed in adolescent girls with hyperandrogenemia, a condition that can lead to adult PCOS. Resistance to feedback by low progesterone levels likely contributes to abnormal GnRH pulses (and abnormal LH/FSH secretion) in these girls, but how this could affect the normal pubertal sequence of GnRH secretion--or how it could contribute to development of PCOS--is unknown.
Specific goals of our group include elucidation of the role of progesterone in directing GnRH secretion and mechanisms controlling diurnal (wake vs. sleep-associated) GnRH pulse frequency in peripubertal girls and women, both in the presence and absence of hyperandrogenemia. Using protocols of frequent hormone sampling and formal sleep analysis, we are testing a working model that involves the primacy of sex steroid negative feedback in the control of GnRH pulse frequency when awake, but the relative inability of sex steroids to influence GnRH pulse frequency during sleep. This model may help explain empirical observations of diurnal gonadotropin dynamics in health and disease, and may also help integrate the “central” and “gonadostat” hypotheses of puberty in girls. Our group also aims to identify mechanisms involved in obesity-associated hyperandrogenemia in peripubertal girls. Specifically, using hyperinsulinemic euglycemic clamp procedures in conjunction with frequent hormone sampling, we aim to define relationships among insulin resistance, hyperinsulinemia, elevated LH, and hyperandrogenemia in obese peripubertal girls. We believe that these studies will enhance our understanding of the mechanisms controlling the normal developmental sequence of GnRH pulse secretion across puberty, and how this sequence is perturbed in the setting of excess testosterone—all with a view to designing rational treatment strategies for the early stages of PCOS.