Estrogen Receptor Alpha Regulates Retinaldehyde Dehydrogenase 1 Expression in Rat Anterior Pituitary Cells

Abstract

Retinoic acid (RA) plays a critical role in embryonic development, growth, and reproduction. RA is synthesized from retinoids via oxidation processes, and the oxidation of retinal to RA is catalyzed by the retinaldehyde dehydrogenases (RALDHs). We previously reported that RALDH1 mRNA was expressed in the anterior pituitary glands of adult rats and suppressed by administration of 17beta-estradiol in vivo. However, little is known about the mechanism regulating pituitary RALDH1 expression. In order to characterize the mechanism of estrogen-induced RALDH1 reduction, we examined the effect of 17beta-estradiol on the regulation of pituitary RALDH1 gene expression and protein production both in vivo and in vitro. Using quantitative real-time PCR and immunoblot analysis, we found that levels of RALDH1 gene expression and protein production markedly decreased after 1-week treatment with 17beta-estradiol in male rats. In immunohistochemical analysis, RALDH1-immunoreaction was observed in prolactin cells and folliculo-stellate cells. In 17beta-estradiol-treated rats, RALDH1-immunoreactivity was lower in prolactin cells, but not in folliculo-stellate cells. Treatment of isolated anterior pituitary cells with 17beta-estradiol (10(-14) - 10(-8) M) decreased expression of RALDH1 mRNA in a dose-dependent manner. Estradiol-induced suppression of RALDH1 expression was completely blocked by the estrogen receptor (ER) antagonist ICI 182, 780. The ERalpha-selective agonist propylpyrazole triol (10(-8) M) mimicked the effect of 17beta-estradiol on RALDH1 expression, but the ERbeta-selective agonist diarylpropionitrile (10(-8) M) did not. These results strongly suggest that RALDH1 mRNA expression is suppressed by 17beta-estradiol through ERalpha, and that estrogen regulates the expression of RALDH1 and production of RA in the anterior pituitary gland.