Novel progestogenic activity of environmental endocrine disruptors in the upregulation of calbindin-D9k in an immature mouse model.
Endocrine disruption is a major global health concern in the industrialized world. The induction of uterine calbindin-D9k (CaBP-9k), which belongs to a large family of intracellular calcium binding proteins, was used to assess the exposure of endocrine disruptors (EDs) in an immature mouse model. Sex steroid hormones have been demonstrated to regulate uterine CaBP-9k expression in the uterus of rats and mice. In particular, the mouse CaBP-9k gene was predominantly regulated by progesterone (P4), whereas rat CaBP-9k was mainly induced by 17-beta-estradiol (E2) in the uterus. In the present study, immature (14-day-old) female mice were injected with 4-tert-octylphenol (OP), nonylphenol (NP), bisphenol A (BPA), E2, or P4 to determine their effects on uterine CaBP-9k mRNA and protein expression. In addition, to specify estrogenic or progestogenic activity of EDs in the regulation of CaBP-9k, the mice were co-treated with ICI 182,780, an estrogen receptor (ER) antagonist, or RU486, a progesterone receptor (PR) antagonist,. Treatments with OP, NP, or BPA resulted in an increase in CaBP-9k mRNA and protein in the uterus of immature mice in a dose-dependent and time-dependent manner. The EDs-induced expression of CaBP-9k mRNA and protein was reversed or abolished by pretreatment with RU486 or ICI 182,780, suggesting that these synthetic chemicals may have both progestogenic and estrogenic properties by acting through PR or ER in the induction of uterine CaBP-9k mRNA and protein in this model. These results describe a novel in vivo model for detection of both estrogenic and progestogenic activities of EDs in the induction of CaBP-9k mRNA and protein in the uterus of immature mice.
Jung
Yong-Woo
YW
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763 Republic of Korea.
Hong
Eui-Ju
EJ
Choi
Kyung-Chul
KC
Jeung
Eui-Bae
EB
D000818:Animals; D001559:Benzhydryl Compounds; D064026:Calbindins; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D000077267:Fulvestrant; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology; D023421:Models, Animal; D010636:Phenols / Q000633:toxicity; D011374:Progesterone / Q000633:toxicity; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*; D013997:Time Factors; D015854:Up-Regulation; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D064026:Calbindins; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D000077267:Fulvestrant; D015735:Mifepristone; D010636:Phenols; D011374:Progesterone; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; C576508:S100g protein, rat; C041594:4-nonylphenol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds