Estrogen receptor-α (ERα), but not ERβ, modulates estrogen stimulation of the ERα-truncated variant, TERP-1

被引:20
|
作者
Schreihofer, DA
Rowe, DF
Rissman, EF
Scordalakes, EM
Gustafsson, JÅ
Shupnik, MA
机构
[1] Univ Virginia, Div Endocrinol & Metab, Dept Internal Med, Charlottesville, VA 22908 USA
[2] Univ Virginia, Dept Biol, Charlottesville, VA 22908 USA
[3] Karolinska Inst, Novum, Dept Med Nutr, S-14186 Huddinge, Sweden
[4] Karolinska Inst, Novum, Ctr Biotechnol, S-14186 Huddinge, Sweden
关键词
D O I
10.1210/en.2002-220353
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Estrogens regulate pituitary gene expression through two nuclear receptors (ERs), ERalpha and ERbeta. Rodent pituitary also expresses high levels of the pituitary-specific ERalpha isoform, truncated ER product-1.(TERP-1), which modulates the response of both ER forms to 17beta-estradiol (E2). Under physiological conditions, E2 stimulates TERP-1 expression from an ERalpha 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 ERalpha (ERalphaKO) or the ERbeta (ERbetaKO) gene was disrupted. TERP-1 mRNA expression was assessed by semi-quantitative RT-PCR, and protein expression was evaluated by immunoblots. Both TERP-1 mRNA and protein were expressed in pituitaries from castrate WT, ERalphaKO, and ERbetaKO male and female mice. E2 stimulated TERP-1 mRNA expression in WT and ERbetaKO mice of both sexes, but had no effect on TERP-1 mRNA in either male or female ERalphaKO mice. Testosterone treatment also stimulated TERP-1 in WT, ERalphaKO, and ERbetaKO male mice. We conclude that ERalpha 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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页码:4196 / 4202
页数:7
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