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Adiponectin Induces Periovulatory Changes in Ovarian Follicular Cells

Centre de Recherche en Reproduction Animale (S.L., D.B.C., F.L.L., M.D.-G., B.D.M.), Faculté de Médecine Vétérinaire, Université de Montréal, Québec, Canada J2S 7C6; Departamento de Cirurgia (D.B.C.), Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, 05508-090 São Paulo, Brazil; and Dairy and Swine Research and Development Center (M.-F.P.), Agriculture and Agri-Food Canada, Lennoxville, Québec, Canada J1M 1Z3

Address all correspondence and requests for reprints to: Bruce D. Murphy, Centre de Recherche en Reproduction Animale, Faculté de Médecine Vétérinaire, Université de Montréal, C.P. 5000, St-Hyacinthe, Québec, Canada J2S 7C6. E-mail: bruce.d.murphy{at}umontreal.ca.

Adiponectin, the most abundantly synthesized protein in adipose tissue, has plieotropic effects on liver, muscle, endothelium, placenta, and other tissues. We examined direct effects of recombinant porcine adiponectin on porcine ovarian granulosa cells in vitro. We demonstrate that adiponectin, at physiologically relevant levels (10–25 µg/ml), provokes expression of genes associated with periovulatory remodeling of the ovarian follicle over a time frame of 6–24 h. These include cyclooxygenase-2, prostaglandin E synthase, and vascular endothelial growth factor. Adiponectin modulates steroid synthetic protein gene expression, increasing steroidogenic acute regulatory protein transcript abundance and reducing cytochrome P450aromatase. Adiponectin has antidiabetic properties and sensitizes tissues to insulin. We show that it interacts with both LH and insulin in inducing expression of cyclooxygenase-2 transcripts in granulosa cells. We determined that the MAPK pathway, via phosphorylation of ERK1/2, is involved in mediation of the adiponectin signal in ovarian granulosa cells, rather than protein kinase A or the classic adiponectin transducer, AMP-activated protein kinase. Adiponectin synthesis is reduced in obesity, and our findings suggest that this reduction plays a role in obesity-related ovarian dysfunction.

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