Christopher R. McCartney, MD
Graduate School: University of Mississippi Medical School
Primary Appointment: Associate Professor, Medicine, Endocrinology and Metabolism
Understanding the Causes of Abnormal Gonadotropin Releasing Hormone (GnRH) Pulses and Abnormal Gonadotropin Secretion in Adolescent and Adult PCOS
Email Address: firstname.lastname@example.org
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. 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. 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.
McCartney CR, Beller JP. Reply. Am J Obstet Gynecol. 2013 Feb 27. doi:pii: S0002-9378(13)00232-9. 10.1016/j.ajog.2013.02.037. [Epub ahead of print] PubMed PMID: 23453803.
Schutt RC, Gordon TA, Bhabhra R, Cathro HP, Cook SL, McCartney CR, Weiss GR. Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report. J Med Case Rep. 2013 Jan 9;7(1):11. doi: 10.1186/1752-1947-7-11. PubMed PMID: 23302323; PubMed Central PMCID: PMC3546898.
Beller JP, McCartney CR. Cardiovascular risk and combined oral contraceptives: clinical decisions in settings of uncertainty. Am J Obstet Gynecol. 2013 Jan;208(1):39-41. doi: 10.1016/j.ajog.2012.01.037. Epub 2012 Feb 1. PubMed PMID: 22360920.
Burt Solorzano CM, Beller JP, Abshire MY, Collins JS, McCartney CR, Marshall JC. Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids. 2012 Mar 10;77(4):332-7. doi: 10.1016/j.steroids.2011.12.007. Epub 2011 Dec 8. Review. PubMed PMID: 22172593; PubMed Central PMCID: PMC3453528.
Abshire MY, Blank SK, Chhabra S, McCartney CR, Eagleson CA, Marshall JC. Role of androgen receptor CAG repeat polymorphism length in hypothalamic progesterone sensitivity in hyperandrogenic adolescent girls. Endocrine. 2012 Feb;41(1):156-8. doi: 10.1007/s12020-011-9563-1. Epub 2011 Nov 13. PubMed PMID: 22081303; PubMed Central PMCID: PMC3253981.
Collins JS, Marshall JC, McCartney CR. Differential sleep-wake sensitivity of gonadotropin-releasing hormone secretion to progesterone inhibition in early pubertal girls. Neuroendocrinology. 2012;96(3):222-7. doi: 10.1159/000336395. Epub 2012 Mar 1. PubMed PMID: 22377800; PubMed Central PMCID: PMC3590818.
Knudsen KL, Blank SK, Burt Solorzano C, Patrie JT, Chang RJ, Caprio S, Marshall JC, McCartney CR. Hyperandrogenemia in obese peripubertal girls: correlates and potential etiological determinants. Obesity (Silver Spring). 2010 Nov;18(11): 2118-24. doi: 10.1038/oby.2010.58. Epub 2010 Mar 25. PubMed PMID: 20339367; PubMed Central PMCID: PMC2932780.
Burt Solorzano CM, McCartney CR. Obesity and the pubertal transition in girls and boys. Reproduction. 2010 Sep; 140(3):399-410. doi: 10.1530/REP-10-0119. Review. PubMed PMID: 20802107; PubMed Central PMCID: PMC2931339.
McCartney CR. Maturation of sleep-wake gonadotrophin-releasing hormone secretion across puberty in girls: potential mechanisms and relevance to the pathogenesis of polycystic ovary syndrome. J Neuroendocrinol. 2010 Jul;22(7):701-9. doi: 10.1111/j.1365-2826.2010.02029.x. Epub 2010 May 12. Review. PubMed PMID: 20492363; PubMed Central PMCID: PMC2908518.
Burt Solorzano CM, McCartney CR, Blank SK, Knudsen KL, Marshall JC. Hyperandrogenaemia in adolescent girls: origins of abnormal gonadotropin-releasing hormone secretion. BJOG. 2010 Jan;117(2):143-9. doi: 10.1111/j.1471-0528.2009.02383.x. PubMed PMID: 20002394; PubMed Central PMCID: PMC2994606.