Estrogen receptor alpha pathway is involved in the regulation of Calbindin-D9k in the uterus of immature rats.
It has been demonstrated in our previous studies that Calbindin-D9k (CaBP-9k) 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 CaBP-9k induction by these compounds through two subtypes of estrogen receptors (ERalpha and ERbeta) is unclear. Thus, in the present study, immature rats were treated with propyl pyrazole triol (PPT, an ERalpha-selective ligand), diarylpropionitrile (DPN, an ERbeta-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 CaBP-9k induction. Following injection with these ER ligands, uterine CaBP-9k expression was analyzed by Northern blot and immunoblot assays. Uterine CaBP-9k expression is mainly mediated by PPT in a dose- and time-dependent manner in immature rats, whereas no significant alteration of the uterine CaBP-9k gene was observed after DPN treatment. In addition, an estrogenicity of PPT in inducing CaBP-9k expression was completely blocked by the anti-estrogen ICI 182,780, implying that uterine CaBP-9k is solely induced by ERalpha. A single treatment with PPT rapidly increased the protein levels of ERalpha and PR, an E2-mediated gene, in these tissues. Taken together, these results indicate that uterine CaBP-9k is induced by E2 and endocrine disrupting chemicals via the ERalpha pathway, but not ERbeta, in the uterus of immature rats.
Lee
Geun-Shik
GS
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763 Republic of Korea.
Kim
Hoe-Jin
HJ
Jung
Yong-Woo
YW
Choi
Kyung-Chul
KC
Jeung
Eui-Bae
EB
D000818:Animals; D064026:Calbindins; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D008024:Ligands; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D064026:Calbindins; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D011980:Receptors, Progesterone; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D000077267:Fulvestrant; D004958:Estradiol; D004121:Dimethyl Sulfoxide