title: Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.
abstract: Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom ; Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
authors.forename: Fabio V
authors.initials: FV
authors.lastname: Comim
authors.forename: Kate
authors.initials: K
authors.lastname: Hardy
authors.forename: Stephen
authors.initials: S
authors.lastname: Franks
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D000728:Androgens / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000378:metabolism*; D011974:Receptors, LH / Q000378:metabolism; D013799:Theca Cells / Q000378:metabolism
chemical_list: D052242:Adiponectin; D000728:Androgens; D054419:Receptors, Adiponectin; D011974:Receptors, LH; D000735:Androstenedione