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.

Cloning of equine prostaglandin dehydrogenase and its gonadotropin-dependent regulation in theca and mural granulosa cells of equine preovulatory follicles during the ovulatory process

“…Indeed, in the primate ovary, PGDH induction occurs in a monophasic manner with a robust induction of PGDH detected at 12 h posthCG and a marked decrease from then to ovulation (ovulation occurs around 40-42 h post-hCG in this species) (Duffy et al 2005). The later induction is restricted only to granulosa cells (Duffy et al 2005). In contrast, our findings indicate that the expression of gonadotropininduced PGDH in the mare was biphasic with strong induction observed at 12 and 33 h after hCG, in both granulosa and theca cells, two main cellular compartments of preovulatory follicles.…”

“…This difference in the pattern of gene regulation is further supported by the present study. Indeed, in the primate ovary, PGDH induction occurs in a monophasic manner with a robust induction of PGDH detected at 12 h posthCG and a marked decrease from then to ovulation (ovulation occurs around 40-42 h post-hCG in this species) (Duffy et al 2005). The later induction is restricted only to granulosa cells (Duffy et al 2005).…”

“…PGDH is an important enzyme involved in PGE2 and PGF2a catabolism. There is only one report on the regulation of PGDH in ovarian physiology of a primate (Duffy et al 2005). However, the information obtained from animal species does not always reflect the spectrum of potential expression among species.…”

“…This process is accompanied with a selective induction of PGHS-2 in granulosa cells and a marked increase in intrafollicular levels of PGE2 and PGF2a (Espey 1980, Watson & Sertich 1990, Sirois & Doré 1997, Watson & Hinrichs 1998. Studies on the regulation of PGDH during ovulation are limited to one recent report from the preovulatory follicle of a primate (Duffy et al 2005). However, studies on the expression and regulation of PGDH in mares are of interest because preovulatory follicular development and ovulation in this animal species show several distinctive characteristics compared with other species, such as a large diameter of the ovulatory follicle (40-45 mm), a relatively long ovulatory process (39-42 h), and the follicular rupture at the ovulatory fossa (Stabenfeldt et al 1975, Duchamp et al 1987, Ginther 1992, Sirois & Doré 1997, Boerboom et al 2000.…”

Evidence that the preovulatory rise in intrafollicular progesterone may not be required for ovulation in cattle

“…Hormonal and cell-specific regulation of PGDH has been examined previously in a primate model, with results distinct from those observed in the present studies. A transient increase in PGDH mRNA was observed in monkey granulosal cells collected 12 h after hCG administration and PGDH protein was localized exclusively to the granulosal layer (Duffy et al 2005). In vitro progesterone treatment of cultured monkey granulosal cells for 24 h did not change PGDH mRNA levels, but 48-h exposure resulted in reduced PGDH mRNA abundance (Duffy et al 2005).…”