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

Estrogens regulate pituitary gene expression through two nuclear receptors (ERs), ERα and ERβ. Rodent pituitary also expresses high levels of the pituitary-specific ERα isoform, truncated ER product-1 (TERP-1), which modulates the response of both ER forms to 17β-estradiol (E2). Under physiological conditions, E2 stimulates TERP-1 expression from an ERα 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 ERα (ERαKO) or the ERβ (ERβKO) 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, ERαKO, and ERβKO male and female mice. E2 stimulated TERP-1 mRNA expression in WT and ERβKO mice of both sexes, but had no effect on TERP-1 mRNA in either male or female ERαKO mice. Testosterone treatment also stimulated TERP-1 in WT, ERαKO, and ERβKO male mice. We conclude that ERα 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.