Ovary

ADRP: A Gonadotropin- and Prostaglandin-Regulated Protein in Primate Periovulatory Follicles

Abstract
The midcycle luteinizing hormone (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 human chorionic gonadotropin (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 if hCG and PGE₂ regulate ADRP expression in vivo, monkeys received gonadotropins to stimulate multiple follicular development. hCG was then administered alone or with the PG synthesis inhibitor celecoxib, and follicular aspirates or whole ovaries were obtained at times which span the 40-hour periovulatory interval. hCG administration 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 when compared to animals treated with hCG only. ADRP was detected by immunocytochemistry in many monkey tissues which synthesize PGs 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 precursor for periovulatory PG production.

Key words: Ovary • Follicle • Granulosa cells • Ovulation

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