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John C. Marshall

John C. Marshall

Andrew D. Hart Professor of Internal Medicine; Director, Center for Research in Reproduction, Medicine- Endocrinology and Metabolism

Primary Location
PO Box 800612
Box 800612 Health Science Ct.
Primary Phone Number
434.924.2431
Fax Number
434.243.6913
Email
[email protected]

Bio & Overview

Dr. Marshall's laboratory has studied the intracellular mechanisms by which Gonadotropin Releasing Hormone (GnRH) stimulates the synthesis of gonadotropin subunits and secretion of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH). These basic studies indicated that the frequency of the GnRH signal differentially regulated gene expression. Recent studies have taken this observation to the clinical level in investigating the disorder of polycystic ovarian syndrome-a common disorder which affects some 7-8% of reproductive-age women and is associated with excess production of male hormone, infertility, obesity, and a tendency in later life to develop diabetes. The disorder is the commonest cause of infertility and abnormal ovulation and appears to develop from the effects of exposure to excess male hormone before and during the pubertal maturational process. This in turn leads to impaired regulation of the frequency of GnRH pulse secretion by steroid hormones. Specifically excess testosterone blocks progesterone inhibition and slowing of GnRH pulse secretion. As a consequence, rapid GnRH pulse signals favor LH synthesis by the pituitary which in turns drives the ovary to maintain the androgen excess. The disorder develops before or during pubertal maturation and in animal models may reflect intrauterine exposure to excess androgen. Our present work focuses on the origins of excess testosterone in pre- and peripubertal girls and has shown that the present epidemic of obesity is associated with increased male hormone levels in 65-70% of obese girls. We believe this triggers abnormal maturation of the steroid-GnRH feedback mechanisms in the hypothalamus with persistence of rapid GnRH secretion and maintenance of the syndrome in adulthood. Present studies are assessing the effects of obesity on adrenal androgen production, the timing of ovarian androgen excess and the duration and degrees of excess androgen required to modify regulation of GnRH secretion. The long-term goals are to inhibit or block excess androgen production prior to any permanent modification of the ovarian steroid-GnRH axis.

Academic Information

Department
Medicine- Endocrinology and Metabolism
Academic Title
Professor

Primary Education

  • BS, Human Neuroanatomy, Victoria University of Manchester (UK), 1962
  • MB ChB, Medicine, Victoria University of Manchester (UK), 1965
  • MRCP, Internal Medicine, Royal College of Physicians (London, UK), 1967
  • MD, Endocrinology, Victoria University of Manchester (UK), 1973

Other Appointments

  • Professor, Medicine
  • Professor, Endocrinology

Other Affiliations

  • Member, Women's Oncology Program
  • Director, Center for Research in Reproduction

Research Interests

Mechanisms of GnRH Regulation of Gonadotropin and Steriod Synthesis; the Etiology of PCOS in Adolescence

Selected Publications

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., 2018; The Journal of clinical endocrinology and metabolism. 103(3) 1112-1121. PMID: 29300925 | PMCID: PMC6283412

Marshall JC McCartney CR, Polycystic Ovary syndrome, 2016; New England Journal of Medicine. 375(1) 54-64. PMID:

Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS, Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome., 2015; Endocrine reviews. 36(5) 487-525. PMID: 26426951 | PMCID: PMC4591526

Collins JS, Marshall JC, McCartney CR, Differential Sleep-Wake Sensitivity of Gonadotropin-Releasing Hormone Secretion to Progesterone Inhibition in Early Pubertal Girls., 2012; Neuroendocrinology. () . PMID: 22377800 | PMCID: PMC3590818

McGee WK, Bishop CV, Bahar A, Pohl CR, Chang RJ, Marshall JC, Pau FK, Stouffer RL, Cameron JL, Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: a possible component of polycystic ovary syndrome., 2011; Human reproduction (Oxford, England). 27(2) 531-40. PMID: 22114112

Burger LL, Haisenleder DJ, Marshall JC, GnRH pulse frequency differentially regulates steroidogenic factor 1 (SF1), dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1 (DAX1), and serum response factor (SRF): potential mechanism for GnRH pulse frequency regulation of LH beta transcription in the rat., 2011; Endocrine. 39(3) 212-9. PMID: 21409515

Jane JA, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO, Marshall JC, Laws ER, Vance ML, Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome., 2011; The Journal of clinical endocrinology and metabolism. 96(9) 2732-40. PMID: 21715544

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., 2011; Endocrine. 41(1) 156-8. PMID: 22081303 | PMCID: PMC3253981

Haisenleder DJ, Schoenfelder AH, Marcinko ES, Geddis LM, Marshall JC, Estimation of estradiol in mouse serum samples: evaluation of commercial estradiol immunoassays., 2011; Endocrinology. 152(11) 4443-7. PMID: 21933867 | PMCID: PMC3198998

Burt Solorzano CM, Beller JP, Abshire MY, Collins JS, McCartney CR, Marshall JC, Neuroendocrine dysfunction in polycystic ovary syndrome., 2011; Steroids. 77(4) 332-7. PMID: 22172593 | PMCID: PMC3453528

Marshall JC, Dunaif A, Should all women with PCOS be treated for insulin resistance?, 2011; Fertility and sterility. 97(1) 18-22. PMID: 22192137 | PMCID: PMC3277302

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., 2010; Obesity (Silver Spring, Md.). 18(11) 2118-24. PMID: 20339367 | PMCID: PMC2932780

Burger LL, Haisenleder DJ, Aylor KW, Marshall JC, Regulation of Lhb and Egr1 gene expression by GNRH pulses in rat pituitaries is both c-Jun N-terminal kinase (JNK)- and extracellular signal-regulated kinase (ERK)-dependent., 2009; Biology of reproduction. 81(6) 1206-15. PMID: 19710510 | PMCID: PMC2788048

Blank SK, McCartney CR, Chhabra S, Helm KD, Eagleson CA, Chang RJ, Marshall JC, Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls--implications for regulation of pubertal maturation., 2009; The Journal of clinical endocrinology and metabolism. 94(7) 2360-6. PMID: 19351732 | PMCID: PMC2708962

McCartney CR, Blank SK, Marshall JC, Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone., 2009; Endocrine. 36(2) 239-45. PMID: 19609733 | PMCID: PMC2758640

Burt Solorzano CM, McCartney CR, Blank SK, Knudsen KL, Marshall JC, Hyperandrogenaemia in adolescent girls: origins of abnormal gonadotropin-releasing hormone secretion., 2009; BJOG : an international journal of obstetrics and gynaecology. 117(2) 143-9. PMID: 20002394

McCartney CR, Prendergast KA, Blank SK, Helm KD, Chhabra S, Marshall JC, Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls., 2008; The Journal of clinical endocrinology and metabolism. 94(1) 56-66. PMID: 18957503 | PMCID: PMC2630866

Blank SK, Helm KD, McCartney CR, Marshall JC, Polycystic ovary syndrome in adolescence., 2008; Annals of the New York Academy of Sciences. 1135() 76-84. PMID: 18574211

Burger LL, Haisenleder DJ, Aylor KW, Marshall JC, Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation., 2008; Biology of reproduction. 79(5) 947-53. PMID: 18716286 | PMCID: PMC2574636

Haisenleder DJ, Burger LL, Walsh HE, Stevens J, Aylor KW, Shupnik MA, Marshall JC, Pulsatile gonadotropin-releasing hormone stimulation of gonadotropin subunit transcription in rat pituitaries: evidence for the involvement of Jun N-terminal kinase but not p38., 2007; Endocrinology. 149(1) 139-45. PMID: 17932215 | PMCID: PMC2194612

Blank SK, McCartney CR, Helm KD, Marshall JC, Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty., 2007; Seminars in reproductive medicine. 25(5) 352-9. PMID: 17710731

Burger LL, Haisenleder DJ, Wotton GM, Aylor KW, Dalkin AC, Marshall JC, The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway., 2007; American journal of physiology. Endocrinology and metabolism. 293(1) E277-85. PMID: 17405825

Helm KD, McCartney CR, Okonkwo QL, Blank SK, Barrett EJ, Marshall JC, Hyperinsulinemia does not acutely enhance adrenal androgen production in women or men., 2007; Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 39(8) 617-9. PMID: 17712728

Blank SK, McCartney CR, Marshall JC, The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome., 2006; Human reproduction update. 12(4) 351-61. PMID: 16670102

McCartney CR, Blank SK, Marshall JC, Progesterone acutely increases LH pulse amplitude but does not acutely influence nocturnal LH pulse frequency slowing during the late follicular phase in women., 2006; American journal of physiology. Endocrinology and metabolism. 292(3) E900-6. PMID: 17122090

McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson CA, Helm KD, Yoo R, Chang RJ, Foster CM, Caprio S, Marshall JC, Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls., 2006; The Journal of clinical endocrinology and metabolism. 92(2) 430-6. PMID: 17118995 | PMCID: PMC2196134

Haisenleder DJ, Aylor KW, Burger LL, Dalkin AC, Marshall JC, Stimulation of FSHbeta transcription by blockade of endogenous pituitary follistatin production: Efficacy of adenoviral-delivered antisense RNA in the rat., 2006; Endocrine. 29(3) 399-404. PMID: 16943576

McCartney CR, Prendergast KA, Chhabra S, Eagleson CA, Yoo R, Chang RJ, Foster CM, Marshall JC, The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism., 2006; The Journal of clinical endocrinology and metabolism. 91(5) 1714-22. PMID: 16492701