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Expression of Ovary-Specific Acidic Protein in Steroidogenic Tissues: A Possible Role in Steroidogenesis

Department of Obstetrics and Gynecology (T.M., K.Min., H.I., M.T., T.T., Y.H., M.F., T.H., S.A., S.H.K., K.Miy., Y.Y.), Keio University School of Medicine, Tokyo, Japan 160-8582; Department of Obstetrics and Gynecology (H.I.), Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan 259-1193; and Oregon National Primate Research Center and Department of Obstetrics and Gynecology (J.D.H.), Oregon Health and Science University, Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Hitoshi Ishimoto, M.D., Ph.D., Department of Obstetrics and Gynecology, Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan 259-1193. E-mail: ishimoto{at}is.icc.u-tokai.ac.jp.

Ovary-specific acidic protein (OSAP) is a novel molecule discovered from a genomic project designed to identify ovary-selective genes in mice. Whereas public databases suggest extraovarian expression of OSAP, its tissue distribution has not yet been well documented. Thus, the expression profile of mouse and human OSAP was determined by quantitative real-time RT-PCR using RNAs isolated from various tissues. The results demonstrate that the human and mouse OSAP expression profiles are similar; OSAP is prominently expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Placenta served as an exception and possessed minimal level of OSAP mRNA. Immunohistochemical studies show that mouse OSAP localizes almost exclusively to the steroid-producing cells of the ovary, adrenal gland, and testis. Consistent with predictions made by several subcellular localization algorithms, dual labeling studies in Y-1 mouse adrenocortical cells indicate OSAP resides in the mitochondria. Because of its abundant expression in steroidogenic cells and mitochondrial localization, a role for OSAP in steroidogenesis was determined. OSAP silencing by specific small interfering RNAs significantly inhibits 8-bromoadenosine-cAMP-induced progesterone production in Y-1 cells. Reduction in OSAP levels results in mitochondrial fragmentation and a decrease in the cellular content of mitochondrial DNA, indicative of decreased mitochondrial abundance. Lastly, 8-bromoadenosine-cAMP does not regulate OSAP protein expression in Y-1 cells as is the case for other steroidogenic components known to be induced by cAMP. Collectively these results suggest that OSAP is involved in steroidogenesis, potentially through its ability to maintain mitochondrial abundance and morphology.