Estrogen Receptor α Pathway Is Involved in the Regulation of <i>Calbindin-D_9k</i> in the Uterus of Immature Rats

다국어 초록 (Multilingual Abstract)

<P>It has been demonstrated in our previous studies that <I>Calbindin-D<SUB>9k</SUB></I> (<I>CaBP-9k</I>) is a potent biomarker for screening estrogen-like chemicals in the rat model. Although treatments with 17beta-estradiol (E2) and endocrine disrupting compounds resulted in the up-regulation of uterine CaBP-9k, the mechanism of <I>CaBP-9k</I> induction by these compounds through two subtypes of estrogen receptors (ERα and ERβ) is unclear. Thus, in the present study, immature rats were treated with propyl pyrazole triol (PPT, an ERα-selective ligand), diarylpropionitrile (DPN, an ERβ-selective ligand), E2, or dimethyl sulfoxide (DMSO, a vehicle control) for three days in order to clarify which subtype of ER is involved in the uterine <I>CaBP-9k</I> induction. Following injection with these ER ligands, uterine <I>CaBP-9k</I> expression was analyzed by Northern blot and immunoblot assays. Uterine <I>CaBP-9k</I> expression is mainly mediated by PPT in a dose- and time-dependent manner in immature rats, whereas no significant alteration of the uterine <I>CaBP-9k</I> gene was observed after DPN treatment. In addition, an estrogenicity of PPT in inducing <I>CaBP-9k</I> expression was completely blocked by the anti-estrogen ICI 182,780, implying that uterine <I>CaBP-9k</I> is solely induced by ERα. A single treatment with PPT rapidly increased the protein levels of ERα and PR, an E2-mediated gene, in these tissues. Taken together, these results indicate that uterine <I>CaBP-9k</I> is induced by E2 and endocrine disrupting chemicals via the ERα pathway, but not ERβ, in the uterus of immature rats.</P>