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Endocrinology Vol. 143, No. 11 4196-4202
Copyright © 2002 by The Endocrine Society

ARTICLE

Estrogen Receptor-{alpha} (ER{alpha}), But Not ERß, Modulates Estrogen Stimulation of the ER{alpha}-Truncated Variant, TERP-1

Derek A. Schreihofer1, Daniel F. Rowe, Emilie F. Rissman, Elka M. Scordalakes, Jan-åke Gustafsson and Margaret A. Shupnik

Division of Endocrinology and Metabolism, Department of Internal Medicine (D.A.S., D.F.R., M.A.S.), and Department of Biology (E.F.R., E.M.S.), University of Virginia, Charlottesville, Virginia 22908; and Center for Biotechnology and Department of Medical Nutrition, Karolinska Institute, NOVUM (J.-Å.G.), S-14186 Huddinge, Sweden

Address all correspondence and requests for reprints to: Margaret A. Shupnik, Ph.D., Box 800578 HSC, University of Virginia, Charlottesville, Virginia 22908. E-mail: mas3x{at}virginia.edu.

Estrogens regulate pituitary gene expression through two nuclear receptors (ERs), ER{alpha} and ERß. Rodent pituitary also expresses high levels of the pituitary-specific ER{alpha} isoform, truncated ER product-1 (TERP-1), which modulates the response of both ER forms to 17ß-estradiol (E2). Under physiological conditions, E2 stimulates TERP-1 expression from an ER{alpha} intronic promoter containing several potential binding sites for ERs. To evaluate the role of intact ER proteins on TERP-1 expression, we measured basal expression and steroid stimulation of TERP-1 in wild-type (WT) mice and mice in which either the ER{alpha} (ER{alpha}KO) or the ERß (ERßKO) gene was disrupted. TERP-1 mRNA expression was assessed by semiquantitative RT-PCR, and protein expression was evaluated by immunoblots. Both TERP-1 mRNA and protein were expressed in pituitaries from castrate WT, ER{alpha}KO, and ERßKO male and female mice. E2 stimulated TERP-1 mRNA expression in WT and ERßKO mice of both sexes, but had no effect on TERP-1 mRNA in either male or female ER{alpha}KO mice. Testosterone treatment also stimulated TERP-1 in WT, ER{alpha}KO, and ERßKO male mice. We conclude that ER{alpha} is critical for E2 stimulation, but not basal expression, of the TERP promoter, and that testosterone may act through the androgen receptor to stimulate the TERP-1 promoter in males.




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