Prostaglandin dehydrogenase and prostaglandin levels in periovulatory follicles: implications for control of primate ovulation by prostaglandin E2

Abstract

Prostaglandin (PG) E2 produced by the periovulatory follicle in response to the midcycle LH surge is essential for successful ovulation in primates. Granulosa cells express the PG synthesis enzyme cyclooxygenase-2 in response to the LH surge, but elevated cyclooxygenase-2 mRNA levels precede rising follicular fluid PGE2 levels by 24 h. Therefore, PG metabolism may play a significant role in regulating follicular concentrations of PGE2 during the periovulatory interval. To test this hypothesis, granulosa cells, follicular fluid, and whole ovaries were obtained from adult monkeys receiving exogenous gonadotropins to stimulate development of multiple, large follicles at times spanning the 40-h periovulatory interval. Ovarian expression of the NAD+-dependent 15-hydroxy PG dehydrogenase (PGDH) was assessed by RT-PCR, Western blotting, and immunohistochemistry. PGDH mRNA levels were low in granulosa cells obtained 0 h after hCG, rose 10-fold 12 h after hCG, and were not different from 0 h by 24-36 h after hCG administration. Granulosa cell PGDH protein was present 0-12 h after hCG but was low/nondetectable 36 h after hCG administration. Follicular fluid PGE2 levels were low at 0-12 h, slightly higher at 24 h, and then rose 10-fold to peak at 36 h hCG. Levels of biologically inactive PGE2 metabolites in follicular fluid were also low at 0 h but elevated at 12-24 h after hCG, times at which PGE2 levels remain low. Therefore, PGDH is present in the primate periovulatory follicle in a pattern consistent with modulation of follicular PGE2 levels during the periovulatory interval, supporting the hypothesis that gonadotropin-regulated PGDH plays a role in the control and timing of ovulation in primates.