Estrogen receptor-alpha (ERalpha), but not ERbeta, modulates estrogen stimulation of the ERalpha-truncated variant, TERP-1.
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 semiquantitative 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.
Schreihofer
Derek A
DA
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Rowe
Daniel F
DF
Rissman
Emilie F
EF
Scordalakes
Elka M
EM
Gustafsson J
Jan-åke
JÅ
Shupnik
Margaret A
MA
D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007438:Introns; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; C118565:TERP-1; D013739:Testosterone; D004958:Estradiol