title: Expression of steroid sulfated transporters and 3β-HSD activity in endometrium of women having polycystic ovary syndrome.
abstract: Intracrinology mechanism involves the metabolism of steroids in peripheral tissues, such as DHEA, to molecules with estrogenic or androgenic activity. Proliferation rate of endometria from Polycystic Ovary Syndrome women (PCOS) is increased, favoring hyperplasia development. Besides, in endometria from PCOS-women the synthesis of androst-5-ene-3β,17β-diol (androstenediol), an estrogenic molecule, is enhanced concomitantly to increased cellular proliferation. DHEA, the major intracrinological precursor, circulates mainly in its sulfated form and requires transporters for cell intake, that belong to the families of organic anion transporting polypeptides (OATP) and organic anion transporters (OAT). The aim of this study was to determine protein levels and activity of sulfated steroid transporters OATP2B1, OATP3A1, OATP4A1 and OAT4 in endometria from control and PCOS-women and to evaluate the activity of the enzyme 3β-HSD. Levels of transporters were done by RT-PCR (OAT4 only) and Western-blot (WB). Additionally, in primary culture cells stimulated with steroids, protein levels by WB and uptake of tritiated DHEAS, were evaluated; 3β-HSD activity was assessed using radiolabel substrate. PCOS-endometrium had higher levels of OATP2B1 and OATP4A1 than CE (p<0.05); decreased OATP4A1 levels were found in androstenediol or testosterone-stimulated cells. Accordingly, the entry of DHEAS to cells was lower in cells stimulated with testosterone (p<0.05); 3β-HSD-activity was similar in control and PCOS-endometria. Therefore, this study describes that steroids can modulate the expression and activity of transporters of OATPs-family in human endometria and that some transporter levels are increased in PCOS-endometria, suggesting a potential role in the pathogenesis of endometrial hyperplasia of these patients.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont #999, Santiago, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Plaza-Parrochia
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont #999, Santiago, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Poblete
authors.affiliation: Department of Pathology, School of Medicine, University of Chile, San Borja Arriarán Clinical Hospital, Santa Rosa #1234, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gabler
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont #999, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carvajal
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont #999, Santiago, Chile.
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero
authors.affiliation: Institute of Nutrition and Food Technology, University of Chile, Macul #5540, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Valladares
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Clinical Hospital, Santos Dumont #999, Santiago, Chile. Electronic address: mvega@med.uchile.cl.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D004717:Endometrium / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D027361:Organic Anion Transporters; D015096:3-Hydroxysteroid Dehydrogenases
keywords: 3βHSD; DHEAS; Endometria; Intracrinology; OAT4; OATP