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Ovarian Stanniocalcin Is Structurally Unique in Mammals and Its Production and Release Are Regulated through the Luteinizing Hormone Receptor

Departments of Physiology (M.P., A.J.W., G.F.W.), Oncology (G.E.D.), and Obstetrics and Gynecology (A.J.W., G.E.D.), Faculty of Medicine and Dentistry, University of Western Ontario, and London Regional Cancer Center (G.E.D.), London, Ontario, Canada N6A 5C1

Address all correspondence and requests for reprints to: Dr. Graham F. Wagner, Department of Physiology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1. E-mail: graham.wagner{at}fmd.uwo.ca.

Stanniocalcin (STC) is a recently discovered mammalian hormone that is widely distributed in many tissues. In rodents the STC gene is most highly expressed in ovary, specifically in androgen-producing thecal and interstitial cells. In addition, ovarian levels of expression rise 15-fold over pregnancy. The objective of this study was to develop a primary culture system for ovarian thecal-interstitial cells (TICs) to identify factors governing STC production and release. We used highly purified primary cultures of rat and bovine TICs, the purity of which was routinely assessed with antigenic and enzymatic markers. The functionality of cells was assured by their responsiveness to LH in the form of progesterone release. We found that forskolin significantly increased STC gene expression and secretion by both rat and bovine TICs, an effect that was only replicated by human (h) chorionic gonadotropin (CG). Coincubation of TICs with hCG and phosphodiesterase inhibitors further increased STC secretion, whereas coincubation of TICs with hCG and protein kinase A inhibitors attenuated hCG-stimulated release. Intriguingly, ovarian STC proved to be substantially larger than the 50-kDa homodimer produced in most other tissues. These results indicate that ovarian STC is physically distinct, a feature that could explain its presence in serum during pregnancy and lactation.

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