Antagonistic actions of estradiol and tamoxifen upon forskolin-dependent meiotic arrest, intercellular coupling, and the cyclic AMP content of hamster oocyte-cumulus complexes.
The effects of estradiol (E2) and the anti-E2 tamoxifen (tam) on forskolin (F)-dependent meiotic arrest in hamster oocytes were investigated. The hypotheses tested were that 1) the arresting action of F is enhanced by E2 and suppressed by tam and 2) the extent of heterologous metabolic coupling and the concomitant transfer of cumulus cell cAMP into the oocyte is increased and decreased by E2 and tam, respectively. E2 was tested with the ID25 F (where ID25 is the dose of F previously shown to arrest the meiosis of 25% cultured oocytes; intact, 3 microM; denuded, 10 microM) and tam was tested with the ID75 F (intact, 10 microM; denuded, 100 microM). E2 induced reversible dose-dependent increases in the percent germinal vesicle (%GV; determined cytogenetically) of both intact and denuded oocytes in the presence of ID25 F (intact: ID50 E2 = 18.0 microM; denuded: ID50 E2 = 17.2 microM) but, in contrast to intact oocytes, E2 also exerted a dose-dependent action on denuded oocytes in the absence of F (ID50 = 26.1 microM). E2 induced dose-dependent increases in the cAMP content (determined by RIA) of intact oocytes (cAMP-oo) and of cumulus masses (cAMP-cm) and in the ratio of cAMPooo:cAMP-cm but failed to elevate F-stimulated cAMP in denuded oocytes. Heterologous metabolic coupling, as assessed by determination of the fraction of radiolabeled uridine marker that was transferred from the cumulus cells to the oocyte, was not significantly enhanced by E2. In contrast to denuded oocytes, tam induced dose-dependent decreases in the %GV and cAMP content of intact oocytes in the presence of ID75 F and significantly depressed heterologous metabolic coupling. While tam failed to antagonize the E2 action on denuded oocytes in the presence of ID25 F, in intact oocytes cultured with E2 and the ID25 F, the anti-E2 significantly decreased the %GV, the cAMP-oo and cAMP-cm, and the extent of heterologous metabolic coupling. These data show that while E2 can directly arrest the maturation of denuded hamster oocytes with no associated elevation of cAMP-oo, E2-enhancement of arrest in intact oocytes is correlated with both elevation of cAMP within the oocyte-cumulus complex and maintenance of heterologous metabolic coupling and is accompanied by an increase in cAMP-oo.
Racowsky
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D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D005576:Colforsin; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D004224:Diterpenes / Q000037:antagonists & inhibitors*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008540:Meiosis / Q000187:drug effects*; D008647:Mesocricetus; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D004224:Diterpenes; D013629:Tamoxifen; D005576:Colforsin; D004958:Estradiol; D000242:Cyclic AMP