title: Inhibitory effects of some possible endocrine-disrupting chemicals on the isozymes of human 11beta-hydroxysteroid dehydrogenase and expression of their mRNA in gonads and adrenal glands.
abstract: The in vitro inhibitory effects of 23 compounds designated as possible endocrine-disrupting chemicals, such as alkylphenols, phthalate esters, phytoestrogens, organotins, and pesticides, on the enzyme activity of the isozymes of human 11beta-HSD, type 1 and 2, were examined. Human liver microsomal 11beta-HSD type 1 was inhibited by 4-nonylphenol (4-NP) and diethylhexyl adipate (IC50 = 49.3 and 49.4 mM, respectively). Further, human kidney microsomal 11beta-HSD type 2 was inhibited by triphenyltin, tributyltin, 4-t-octylphenol, 4-NP, 4-n-octylphenol, 4-n-nonylphenol, and dicyclohexyl phthalate (IC50 = 3.3, 16.5, 8.9, 20.3, 23.5, 26.2 and 46.5 microM, respectively). The other chemicals studied did not significantly inhibit the enzyme at concentrations lower than 50 microM. The expression of mRNA of the isozymes in gonads, accessory genital glands, and adrenal glands were investigated by RT-PCR. 11beta-HSD type 1 was detected in human testis, ovary, and prostate. The level in the adrenal gland(s) was similar to that in the liver, which is known to be expressed in large quantities. In contrast, except for the prostate, only small amounts of the 11beta-HSD type 2 isozyme were detected in these human tissues compared to kidney.
authors.affiliation: Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ohshima
authors.forename: Shuji
authors.initials: S
authors.lastname: Ohno
authors.forename: Shizuo
authors.initials: S
authors.lastname: Nakajin
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006066:Gonads / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009928:Organ Specificity; D010053:Ovary / Q000201:enzymology; D011467:Prostate / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000201:enzymology
chemical_list: D052244:Endocrine Disruptors; D007527:Isoenzymes; D012333:RNA, Messenger; D042842:11-beta-Hydroxysteroid Dehydrogenases