title: Steroid sulfatase mediated growth Sof human MG-63 pre-osteoblastic cells.
abstract: Estrogen plays an important role in maintaining bone density. Postmenopausal women have low plasma estrogen, but have high levels of conjugated steroids, particularly estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHEAS). Conversion of these precursors to active estrogens may help maintain bone density in postmenopausal women. The enzyme steroid sulfatase (STS) converts sulfated steroids into active forms in peripheral tissues. STS occurs in bone, but little is known about its role in bone function. In this study, we investigated STS activity and expression in the human MG-63 pre-osteoblastic cell line. We also tested whether sulfated steroids can stimulate growth of these cells. MG-63 cells and microsomes both possessed STS activity, which was blocked by the STS inhibitors EMATE and 667 Coumate. Further evidence for STS in these cells was provided by RT-PCR, using STS specific primers, which resulted in cDNA products of the predicted size. We then tested for growth of MG-63 cells in the presence of estradiol-17β, E1S and DHEAS. All three steroids stimulated MG-63 cell growth in a steroid-free basal medium. We also tested whether the cell growth induced by sulfated steroids could be blocked using a STS inhibitor (667 Coumate) or using an estrogen receptor blocker (ICI 182,780). Both compounds inhibited E1S-induced cell growth, indicating that E1S stimulates MG-63 cell growth through a mechanism involving both STS and the estrogen receptor. Finally, we demonstrated using RT-PCR that MG-63 cells contain mRNA for both estrogen receptor alpha and estrogen receptor beta. Our data reveal that STS is present in human pre-osteoblastic bone cells and that it can influence bone cell growth by converting inactive sulfated steroids to estrogenic forms that act via estrogen receptor alpha or beta.
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Dias
authors.affiliation: Department of Biological Sciences, Duquesne University, Pittsburgh, PA, USA. Electronic address: selcer@duq.edu.
authors.forename: K W
authors.initials: KW
authors.lastname: Selcer
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D000077267:Fulvestrant; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D000077267:Fulvestrant; D004970:Estrone; D004958:Estradiol; D043266:Steryl-Sulfatase; C017296:estrone sulfate
keywords: Bone; Dehydroepiandrosterone sulfate; Estrogens; Estrone sulfate; Osteoblast; Steroid sulfatase