Christopher R. McCartney, MD
Associate Professor of Medicine
Endocrinology and Metabolism
- Undergraduate: B.S. (Biology), Mississippi College, Clinton, MS
- Graduate: M.D., University of Mississippi School of Medicine, Jackson, MS
- Internal Medicine Residency, University of Mississippi Medical Center, Jackson, MS
- Endocrinology Fellowship, University of Virginia Health System, Charlottesville, VA
- Graduate: M.S. (Health Evaluation Sciences/Clinical Research), University of Virginia Health System
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/LH secretion and mechanisms controlling wake vs. sleep-associated GnRH/LH 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/LH pulse frequency when awake, but the relative inability of sex steroids to influence GnRH/LH 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/LH 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.
Our work is currently funded by NIH P50 HD28934 (Eunice Kennedy Shriver NICHD Specialized Cooperative Centers Program in Reproduction and Infertility Research, Marshall PI Master, McCartney PI Project 1, “Testosterone-GnRH Frequency and the Evolution of PCOS in Adolescence,” 04/01/14–03/31/19.
A selection of recent publications (updated August 2018)
- Burt Solorzano CM, Knudsen KL, Anderson AD, Hutchens EG, Collins JS, Patrie JT, Marshall JC, McCartney CR. Insulin resistance, hyperinsulinemia, and LH: relative roles in peripubertal obesity-associated hyperandrogenemia. J Clin Endocrinol Metab 2018; 103: 2571–2582
- Kim SH, Burt Solorzano CM, McCartney CR. Progesterone administration does not acutely alter LH pulse secretion in the mid-follicular phase in women. Physiol Rep 2018; 6(7). pii: e13680
- Lu C, Hutchens EG, Farhi LS, Bonner HG, Suratt PM, McCartney CR. Influence of sleep stage on sleep-associated LH pulse initiation in normal mid- to late follicular phase women and in women with polycystic ovary syndrome. Neuroendocrinology 2018 107: 60-72
- Kim SH, Lundgren JA, Bhabhra R, Collins JS, Patrie JT, Burt Solorzano CM, Marshall JC, McCartney CR. Progesterone-mediated inhibition of the GnRH pulse generator: differential sensitivity as a function of sleep status. J Clin Endocrinol Metab 2018; 103: 1112–1121
- Lundgren JA, Kim SH, Burt Solorzano CM, McCartney CR, Marshall JC. Progesterone suppression of LH pulse frequency in adolescent girls with hyperandrogenism: effects of metformin. J Clin Endocrinol Metab 2018; 103: 263-270
- McCartney CR, Marshall JC. Neuroendocrinology of Reproduction. (Chapter 1) In Strauss JF and Barbieri RL (eds), Yen & Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management, 8th edition, Elsevier Saunders, Philadelphia, PA, 2018
- Burt Solorzano CM, Helm KD, Patrie JT, Shayya RF, Cook-Andersen HL, Chang RJ, McCartney CR, Marshall JC. Increased adrenal androgens in overweight peri-pubertal girls. J Endocr Soc 2017; 1: 538-552
- Hutchens EG, Ramsey KA, Howard LC, Abshire MY, Patrie JT, McCartney CR. Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 hours in estradiol-pretreated women. Physiol Rep 2016 Aug; 4(16). pii: e12891
- McCartney CR, Marshall JC. CLINICAL PRACTICE. Polycystic ovary syndrome. N Engl J Med 2016; 375: 54-64