title: In vivo regulation of steroid hormones by the Chst10 sulfotransferase in mouse.
abstract: Chst10 adds sulfate to glucuronic acid to form a carbohydrate antigen, HNK-1, in glycoproteins and glycolipids. To determine the role of Chst10 in vivo, we generated systemic Chst10-deficient mutant mice. Although Chst10(-/-) mice were born and grew to adulthood with no gross defects, they were subfertile. Uteri from Chst10(-/-) females at the pro-estrus stage were larger than those from wild-type females and exhibited a thick uterine endometrium. Serum estrogen levels in Chst10(-/-) females were higher than those from wild-type females, suggesting impaired down-regulation of estrogen. Because steroid hormones are often conjugated to glucuronic acid, we hypothesized that Chst10 sulfates glucuronidated steroid hormone to regulate steroid hormone in vivo. Enzymatic activity assays and structural analysis of Chst10 products by HPLC and mass spectrometry revealed that Chst10 indeed sulfates glucuronidated estrogen, testosterone, and other steroid hormones. We also identified an HPLC peak corresponding to sulfated and glucuronidated estradiol in serum from wild-type but not from Chst10 null female mice. Estrogen-response element reporter assays revealed that Chst10-modified estrogen likely did not bind to its receptor. These results suggest that subfertility exhibited by female mice following Chst10 loss results from dysregulation of estrogen. Given that Chst10 transfers sulfates to several steroid hormones, Chst10 likely functions in widespread regulation of steroid hormones in vivo.
authors.affiliation: Glycobiology Unit, Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors.forename: Misa
authors.initials: M
authors.lastname: Suzuki-Anekoji
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Sz-Wei
authors.initials: SW
authors.lastname: Wu
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Angata
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugihara
authors.forename: Tomoya O
authors.initials: TO
authors.lastname: Akama
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D004967:Estrogens / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D020723:Glucuronic Acid / Q000737:chemistry; D006017:Glycolipids / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D011995:Recombination, Genetic; D013256:Steroids / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D000097811:Carbohydrate Sulfotransferases
chemical_list: D004967:Estrogens; D020723:Glucuronic Acid; D006017:Glycolipids; D013256:Steroids; D015238:Sulfotransferases; D013739:Testosterone; C499545:Chst10 protein, mouse; D000097811:Carbohydrate Sulfotransferases