Jean Wilson, MD

Professor Emeritus
Internal Medicine

Contact Information

UT Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, Texas 75390

jean.wilson@utsouthwestern.edu

Biography

Dr. Wilson as a student studied the control of urinary acid secretion by adrenal hormones as as a resident investigated cholesterol metabolism. At the NIH he studied ethanolamine biosynthesis, since 1960 he has been in the Department of Internal Medicine at UT Southwestern. In 1970 he worked at Cambridge University, and he has collaborated since 1985 with Marilyn B. Renfree in Melbourne investigating sexual differentiation in marsupials. His research has focused on two problems. The cholesterol project (1960-72)developed methods for quantification of cholesterol synthesis, absorption, degradation, and excretion in intact animals. Demonstration that plasma cholesterol is synthesized in the intestinal wall and liver led to development of paradigms to define the contributions of diet and endogenous synthesis to cholesterol turnover in humans and baboons. The hormone action project (1960-) stemmed from his student research experience, and the dramatic response of the male urogenital tract to testosterone provided a useful model system to investigate hormone action. In the initial studies, testosterone increased protein synthesis in the rat seminal vesicle after enhancement of mRNA formation. The Wilson group showed that radioactive testosterone localizes in the nuclei of target cells, preferentially at the site of MRNA synthesis. Nicholas Bruchovsky in the laboratory defined conditions for extraction of nuclear pellets from so that 40% of the radioactivity remained bound to macromolecules, but most of the bound radioactivity was in the 5a-reduced metabolite of testosterone, dihydrotestosterone (DHT). DHT is bound to a protein component of the chromatin, indicating that the androgen receptor is protein. These findings mandated reexamination of androgen physiology. Testosterone plays three inital roles; it controls luteinizing hormone formation, spermatogenesis, and Wolffian duct virilization. DHT mediates formation of the prostate, male urethra, and phallus and most aspects of virilization at puberty. Ongoing studies indicate that another 5a-reduced androgen (5a-androstane-3a,17b-diol) virilizes tammar wallaby pouch young and is formed in immature mouse tests and is converted in target tissues to DHT. Thus, DHT is formed by two mechanisms. His group then investigated the disorders that impair male development (male pseudohermaphroditism). Fibroblasts cultured from genital skin were utilized to characterize mutations of steroid 5a-reductase 2, the androgen receptor, testosterone synthesis, and the luteinizing hormone receptor. Ultimately, the cDNAs for these proteins were cloned by his colleagues, and gene maps for the mutations were assembled. Another disorder results from the conversion of testosterone to a contradictory hormone, estradiol, and mutations that increase estrogen formation to cause the feminization of roosters and (as shown by others) men. Benign prostatic hyperplasia is a disorder of androgen excess. In most species DHT formation declines and prostate growth ceases after sexual maturation, but in aging men and dogs continued prostate growth can eventuate in obstruction of the urethra and/or rectum. Penti K. Siiteri and Wilson found that DHT levels are high in hyperplastic prostates of both species. Hormone regimens that increase DHT levels induce prostatic hyperplasia in castrated dogs, and inhibition of 5a-reductase causes regression of established prostatic hyperplasia in dogs. In men 5a-reductase inhibition decreases prostatic DHT levels, decreases prostatic volume and prevents further growth, increases urine flow and decreases urinary retention and surgical interventions. In summary, studies of androgen action provide insight into defects of androgen production/action and the effects of unregulated androgen action.

Education

Graduate SchoolUniversity of Texas Southwestern Med Ctr Dallas (1955)

Research Interests

Benign prostatic hyperplasia
Extraglandular aromatization
Male pseudohermaphroditism
Mechanism of androgen action
Sexual differentiation

Publications

Formation of 5-reduced androgens in the testes and urogenital tract of the grey short-tailed opossum, Monodelphis domestica

Wilson JD, Renfree MB, Auchus RJ, Pask AJ, Shaw G , Reproduction, Fettility and Development , Spring 2009; (21):649-654

Wolffian duct differentiation by physiological concentrations of androgen delivered systemically

Renfree MB, Fenelon J, Wijiyanti G, Wilson JD, Shaw G , Developmental Biology , Spring 2009; (334):429-436

Report of fertility in a woman with a predominantly 46, XY karyotype in a family with multiple disorders of sexual development

Dumic M, Lin-Su K, Leibel NI, Ciglar S, Vinci G, Lasan R, Nimkarn S, Wilson JD, McElreavy K, New MI , The Journal of Clinical Endocrinology & Metabolism , Spring 2008; (93):182-189

Role of the alternate pathway of dihydrotestosterone formation in virilization of the Wolffian ducts of the tammar wallaby, Macropus eugenii

Shaw G, Fenelon J, Sichlau M, Auchus RJ, Wilson JD, Renfree MB , Endocrinology , Spring 2006; (147):2368-2373

Ontogeny and pathway of formation of 5-androstane-3,17-diol in the testes of the immature brushtapossum Trichosurus vulpeculail

Wilson JD, Shaw G, Renfree MB, Auchus RJ, Leihy MW, Eckery DC , Reproduction, Fertility and Development , Spring 2005; (17):603-609

Honors/Awards

Kober Medal, Association of American Physicians

(1999)

Fred Conrad Koch Award, The Endocrine Society

(1993)

Gregory Pincus Award, Worcester Foundation for Experimental Biology

(1992)

Henry Dale Medal, Society for Endocrinology

(1991)

Amory Prize, American Academy of Arts and Sciences

(1977)

Professional Associations/Affiliations

American Academy of Arts and Sciences

American Philosophical Society

Fellow of the Royal College of Physicians

Institute of Medicine of the National Academy of Sciences

National Academy of Sciences