The role of protein kinase-c in gonadotropin-induced ovulation in the in vitro perfused rabbit ovary

G. Kaufman, A. M. Dharmarajan, Y. Takehara, C. S. Cropp, E. E. Wallach

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor-promoting phorbol esters are believed to affect ovarian granulosa cell progesterone and prostaglandin (PG) production and possibly ovulation by activating protein kinase-C (PKC). The effects of phorbol esters and PKC inhibitors on ovulation, progesterone, and PG production were examined in an in vitro perfused rabbit ovary. The effect of tranexamic acid, an inhibitor of the conversion of plasminogen activator to plasmin, on phorbol ester-induced ovulation was also examined. Phorbol 12,13-dibutyrate (PdBU), a PKC stimulator, induced ovulation in a dose-related manner in the absence of gonadotropins (567, 200 nM PdBU; 07, 0 nM PdBU; P< 0.05). Perfusate progesterone levels were increased only after 600 nM PdBU treatment, and perfusate PGF, PGE2, and 6-keto-PGF, were increased in a dose-dependent fashion (P < 0.05). Staurosporine, a potent inhibitor of the catalytic domain of PKC, and calphostin-C, a specific inhibitor of the diacyl-glycerol-binding region, inhibited hCG-induced ovulation in a dose- related manner. Gonadotropin-induced ovulation decreased from 737 without staurosporine to 197 with 1.0 ftM staurosporine (P < 0.01). Calphostin-C reduced ovulatory efficiency from 607 to 247 (P < 0.01). However, neither inhibitor decreased progesterone or PGF, production by ovaries exposed to hCG. hCG-induced oocyte maturation was also unaffected by exposure to either staurosporine or calphostin-C. Tranexamic acid reduced phorbol ester-induced ovulatory efficiency from 677 to 377 (P < 0.05). These findings demonstrate that the calcium- dependent PKC pathway is instrumental in gonadotropin-mediated follicular rupture in the rabbit. Although PGs may play an important role in ovulation, they do not appear to be directly responsible for PKC-mediated follicular rupture.

Original languageEnglish (US)
Pages (from-to)1804-1809
Number of pages6
JournalEndocrinology
Volume131
Issue number4
DOIs
StatePublished - Oct 1992

ASJC Scopus subject areas

  • Endocrinology

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