Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
Endocr J. 2009;56(8):963-73. doi: 10.1507/endocrj.k09e-115. Epub 2009 Aug 11.
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.
视黄酸（RA）在胚胎发育、生长和生殖中起着关键作用。RA 是通过氧化过程从类视黄醇合成的，视网膜醛脱氢酶（RALDHs）催化视网膜向 RA 的氧化。我们之前报道过，RALDH1mRNA 在成年大鼠的垂体前叶中表达，并在体内被 17β-雌二醇给药抑制。然而，关于调节垂体 RALDH1 表达的机制知之甚少。为了描述雌激素诱导的 RALDH1 减少的机制，我们检查了 17β-雌二醇对体内和体外调节垂体 RALDH1 基因表达和蛋白产生的影响。使用定量实时 PCR 和免疫印迹分析，我们发现，在雄性大鼠接受 17β-雌二醇治疗 1 周后，RALDH1 基因表达和蛋白产生水平显著降低。在免疫组织化学分析中，RALDH1 免疫反应见于催乳素细胞和滤泡星状细胞。在 17β-雌二醇处理的大鼠中，RALDH1 免疫反应在催乳素细胞中降低，但在滤泡星状细胞中没有降低。用 17β-雌二醇（10（-14）-10（-8）M）处理分离的垂体前体细胞以剂量依赖性方式降低 RALDH1mRNA 的表达。雌激素受体（ER）拮抗剂 ICI 182,780 完全阻断了雌二醇诱导的 RALDH1 表达的抑制。ERα 选择性激动剂丙基吡唑三醇（10（-8）M）模拟了 17β-雌二醇对 RALDH1 表达的作用，但 ERβ 选择性激动剂二芳基丙腈（10（-8）M）没有。这些结果强烈表明，RALDH1mRNA 表达受 17β-雌二醇通过 ERα 抑制，雌激素调节垂体前叶 RALDH1 的表达和 RA 的产生。
