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Adipose Differentiation-Related Protein: A Gonadotropin- and Prostaglandin-Regulated Protein in Primate Periovulatory Follicles¹

Department of Physiological Sciences,³ Eastern Virginia Medical School, Norfolk, Virginia 23507; California National Primate Research Center Department of Obstetrics and Gynecology,⁴ University of California, Davis, California 95616

The midcycle LH surge stimulates a rise in follicular fluid prostaglandin E₂ (PGE₂), which is necessary for normal ovulation. To examine PGE₂-regulated processes in primate follicles, monkey granulosa cells were cultured with hCG alone or with hCG and PGE₂, and the resulting total RNA was subjected to microarray analysis. Twenty PGE₂-regulated mRNAs were identified, and we selected a lipid droplet protein, adipose differentiation-related protein (ADRP), for further study. To determine whether hCG and PGE₂ regulate ADRP expression in vivo, monkeys received gonadotropins to stimulate multiple follicular development. Human chorionic gonadotropin was then administered alone or with the PG synthesis inhibitor celecoxib, and follicular aspirates or whole ovaries were obtained at times that span the 40-h periovulatory interval. Administration of hCG increased granulosa cell ADRP mRNA and protein, with peak levels measured just before the expected time of ovulation. Treatment with hCG and celecoxib decreased granulosa cell ADRP mRNA levels compared with those of animals treated with hCG only. ADRP was detected by immunocytochemistry in many monkey tissues that synthesize prostaglandins but was not consistently expressed by steroidogenic tissues. Granulosa cells of periovulatory follicles immunostained for ADRP after, but not before, hCG administration; ADRP colocalized with large lipid droplets within the granulosa cell cytoplasm. These studies identify ADRP as a novel gonadotropin- and PGE₂-regulated protein in the granulosa cells of primate periovulatory follicles. Because ADRP facilitates arachidonic acid uptake in nonovarian cells, ADRP-associated lipid droplets may enhance arachidonic acid uptake by granulosa cells to provide a precursor for periovulatory prostaglandin production.

adipose differentiation-related protein, follicle, granulosa cells, monkey, ovary, ovulation

² Correspondence: Diane M. Duffy, Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk VA 23507. FAX: 757 624 2269; duffydm{at}evms.edu

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