This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Couse, J. F. Articles by Korach, K. S. Search for Related Content PubMed PubMed Citation Articles by Couse, J. F. Articles by Korach, K. S.

The Intraovarian Actions of Estrogen Receptor- Are Necessary to Repress the Formation of Morphological and Functional Leydig-Like Cells in the Female Gonad

Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology (J.F.C., M.M.Y., K.F.R., K.S.K.), Laboratory of Experimental Pathology (J.A.J.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; and Medicinal Chemistry Division (D.P.), Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Quebec, Sainte-Foy, Quebec, Canada G1V 4G2

Address all correspondence and requests for reprints to: Dr. Kenneth S. Korach, Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, MD B3-02, P.O. Box 12233, Research Triangle Park, North Carolina 27709. E-mail: korach{at}niehs.nih.gov.

The predisposition of the testis and ovary to primarily synthesize testosterone (T) and estradiol (E2), respectively, is due to gonadal-specific cell types that differentially express the various hydroxysteroid (17ß) dehydrogenase (HSD17B) isoforms. In testes, Leydig cells rely on LH stimulation to maintain expression of the type 3 (HSD17B3) isoform, which specifically converts androstenedione to T. In ovaries, thecal interstitial (TI) cells also rely on LH to induce androgen synthesis but lack HSD17B3 and therefore secrete androgens of low biological activity. Therefore, thecal cells may possess a mechanism to repress the Leydig cell phenotype and HSD17B3 expression. E2 is known to inhibit experimentally Leydig cell function and proliferation. In the current study, we provide evidence that E2 prevents the development of functional Leydig-like cells in the murine ovary and that this action is mediated by estrogen receptor (ER) . ER-null (ERKO) female mice exhibit testis-like levels of Hsd17b3 expression in the ovaries and male-like levels of plasma T. Herein, we demonstrate that: 1) Hsd17b3 expression in ERKO ovaries is a primary effect of the loss of intraovarian ER actions; 2) ERKO ovarian cells produce substantial levels of T in vitro, and this is blocked by a HSD17B3-specific inhibitor; 3) Hsd17b3 expression in ERKO ovaries is LH regulated and localized to the secondary interstitial (SI)/TI cells; and 4) ERKO SI/TI cells possess Leydig-like ultrastructural features. These data indicate that intraovarian ER actions are required to repress Hsd17b3 expression in the ovary and may be important to maintaining a female phenotype in SI/TI cells.

This article has been cited by other articles:

				F. Taniguchi, J. F. Couse, K. F. Rodriguez, J. M. A. Emmen, D. Poirier, and K. S. Korach Estrogen receptor-{alpha} mediates an intraovarian negative feedback loop on thecal cell steroidogenesis via modulation of Cyp17a1 (cytochrome P450, steroid 17{alpha}-hydroxylase/17,20 lyase) expression FASEB J, February 1, 2007; 21(2): 586 - 595. [Abstract] [Full Text] [PDF]

				M. Poutanen Toward understanding the endocrine regulation of gonadal somatic cells. Endocrinology, August 1, 2006; 147(8): 3662 - 3665. [Full Text] [PDF]