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

Abstract

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 17β-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 17β-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 17β-estradiol in male rats. In immunohistochemical analysis, RALDH1-immunoreaction was observed in prolactin cells and folliculo-stellate cells. In 17β-estradiol-treated rats, RALdh1-immunoreactivity was lower in prolactin cells, but not in folliculo-stellate cells. treatment of isolated anterior pituitary cells with 17β-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 ERα-selective agonist propylpyrazole triol (10 -8 M) mimicked the effect of 17β-estradiol on RALDH1 expression, but the ERβ-selective agonist diarylpropionitrile (10 -8 M) did not. these results strongly suggest that RALDH1 mRNA expression is suppressed by 17β-estradiol through ERα, and that estrogen regulates the expression of RALdh1 and production of RA in the anterior pituitary gland.

Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes

“…Raldh1 , which encodes the RA synthetic enzyme retinaldehyde dehydrogenase 1 present in tanycytes (Shearer et al, 2010), was investigated as a gene regulated by several nuclear receptor family members (Fujiwara et al, 2009; Huq et al, 2006; MacLean et al, 2008). This gene was significantly upregulated in the hypothalamus of T3‐treated rats (Fig.…”

“…However despite considerable investigation, the genes directly regulated by TH in the hypothalamus are largely unknown; indeed, the genes regulated by TH in much of the brain remain undiscovered. Retinaldehyde dehydrogenase 1 (Raldh1, also known as Aldh1a1) is regulated by a number of hormone activators of nuclear receptors, such as estrogen (Fujiwara et al, 2009) and androgen (MacLean et al, 2008), as well as metabolite‐regulated nuclear receptors such as LXR (Huq et al, 2006). Via its synthesis of retinoic acid (RA) from retinaldehyde, Raldh1 itself then controls the activity of further nuclear receptors, the retinoic acid receptors (RARs).…”

Effect of retinoic acid on midkine gene expression in rat anterior pituitary cells

“…Visualization of MK mRNA was performed with alkaline phosphatase-conjugated anti-DIG antibody (Roche Diagnostics) by using 4-nitroblue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl phosphate (Roche Diagnostics). For double-staining, after detection of MK mRNA by in situ hybridization, the section was immunostained with an antibody for rat RALDH1 [3], as described in our previous report [2]. The ABC method (Vector Laboratories, Burlingame, CA, USA) was used, with 3,3′-diaminobenzidine (Dojindo Laboratories, Kumamoto, Japan) as the substrate.…”

Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

“…Total RNAs were extracted with an RNeasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Quantitative real-time PCR was performed as described in our previous report [11]. cDNA was synthesized by a PrimeScript First Strand cDNA Synthesis Kit (Takara Bio, Otsu, Japan).…”

“…Primary cell culture was performed according to our previous report [11]. Rats aged 9-10 weeks were perfused with Ca 2+ -and Mg…”