This Research Career Award will support the development of Christopher R. McCartney, M.D., of the University of Virginia (UVa) as he continues to train in patient-oriented research under the mentorship of John C. Marshall, M.D., Ph.D., a renowned researcher in the fields of reproductive neuroendocrinology and the polycystic ovary syndrome (PCOS). This training will allow Dr. McCartney to acquire the knowledge and skills needed by an independent clinical researcher. To this end, the application outlines a career development plan that includes comprehensive instruction in clinical trials methodology, biostatistics, epidemiology, research ethics, assay methodology, and hormone pulse analysis; this will occur in part through the Master of Science Program in the UVa Dept. of Health Evaluation Sciences. Dr. McCartney's research proposal is designed to enhance understanding of the etiology of neuroendocrine abnormalities in PCOS, a very common but enigmatic disorder marked by hyperandrogenism, ovulatory dysfunction, and decreased fertility. Although the etiology of PCOS is unknown, relative gonadotropin-releasing hormone (GnRH) pulse generator resistance to negative feedback by progesterone (P) and estradiol (E2) contributes to a persistently rapid luteinizing hormone (LH) pulse frequency, ovulatory dysfunction, and hyperandrogenemia. GnRH pulse generator resistance to negative feedback may also be present in adolescents with hyperandrogenemia, felt to be a forerunner of adult PCOS; this would, in part, explain the pubertal genesis of abnormal LH secretion in adolescents destined to develop PCOS. The specific goals of this research are to delineate the relative roles of P and E2 in the regulation of the GnRH pulse generator throughout ovulatory menstrual cycles; to elucidate the potential role of P in directing diurnal changes of LH (and by inference GnRH) pulsatility in peripubertal adolescent girls; and to define abnormalities of gonadal steroid feedback on the GnRH pulse generator in hyperandrogenemic adolescents and in adults with PCOS. The research will be performed in a state-of-the-art General Clinical Research Center at UVa and, in conjunction with didactic training in scientific inquiry and data analysis, will permit Dr. McCartney's development into an independent patient-oriented investigator in the field of reproductive endocrinology. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HD044742-01
Application #
6675842
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Parrott, Estella C
Project Start
2003-09-01
Project End
2008-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$126,255
Indirect Cost
Name
University of Virginia
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Abshire, Michelle Y; Blank, Susan K; Chhabra, Sandhya et al. (2012) Role of androgen receptor CAG repeat polymorphism length in hypothalamic progesterone sensitivity in hyperandrogenic adolescent girls. Endocrine 41:156-8
Collins, Jessicah S P; Marshall, John C; McCartney, Christopher R (2012) Differential sleep-wake sensitivity of gonadotropin-releasing hormone secretion to progesterone inhibition in early pubertal girls. Neuroendocrinology 96:222-7
Knudsen, Karen L; Blank, Susan K; Burt Solorzano, Christine et al. (2010) Hyperandrogenemia in obese peripubertal girls: correlates and potential etiological determinants. Obesity (Silver Spring) 18:2118-24
McCartney, C R (2010) 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 22:701-9
McCartney, Christopher R; Prendergast, Kathleen A; Blank, Susan K et al. (2009) Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls. J Clin Endocrinol Metab 94:56-66
Blank, Susan K; McCartney, Christopher R; Chhabra, Sandhya et al. (2009) Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls--implications for regulation of pubertal maturation. J Clin Endocrinol Metab 94:2360-6
McCartney, Christopher R; Blank, Susan K; Marshall, John C (2009) Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone. Endocrine 36:239-45
McCartney, Christopher R; Stukenborg, George J (2008) Decision analysis of discordant thyroid nodule biopsy guideline criteria. J Clin Endocrinol Metab 93:3037-44
McCartney, Christopher R; Blank, Susan K; Prendergast, Kathleen A et al. (2007) Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J Clin Endocrinol Metab 92:430-6
Helm, K D; McCartney, C R; Okonkwo, Q L et al. (2007) Hyperinsulinemia does not acutely enhance adrenal androgen production in women or men. Horm Metab Res 39:617-9

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