Prostaglandin dehydrogenase (PGDH) in granulosa cells of primate periovulatory follicles is regulated by the ovulatory gonadotropin surge via multiple G proteins

Abstract

The ovulatory gonadotropin surge increases granulosa cell prostaglandin synthesis as well as prostaglandin dehydrogenase (PGDH), the key enzyme responsible for prostaglandin metabolism. To investigate gonadotropin regulation of PGDH in the primate follicle, monkey granulosa cells were obtained across the 40-h periovulatory interval. PGDH activity was low before the ovulatory hCG stimulus, peaked 12-24 h after hCG, and was low again 36 h after hCG administration. Granulosa cells maintained in vitro with hCG showed a similar temporal pattern of PGDH. The LH/CG receptor can utilize multiple signaling pathways to regulate intracellular events. Gonadotropin-stimulated cAMP appears to act primarily via the Epacs to increase PGDH mRNA, protein, and activity. In contrast, PLC activation of PKC likely decreases PGDH mRNA, protein, and activity late in the periovulatory interval. Increased, then decreased PGDH activity may delay accumulation of prostaglandins in the follicle until late in the periovulatory interval, contributing to timely ovulation in primates.