Gonadotropin-induced accumulation of 4,4-dimethylsterols in mouse ovaries and its temporal relation to meiosis

The resumption of oocyte meiosis is triggered by a number of 4,4-dimethylst erols termed meiosis-activating sterols (MAS). The levels of meiosis active (follicular fluid [FF]-MAS and bull testes [T]-MAS) and inactive (lanoster ol) 4,4-dimethylsterols, free cholesterol, and progesterone were determined in gonadotropin-primed prepubertal mouse ovaries in vivo by high-performan ce liquid chromatography. Ovaries responded to an ovulatory stimulation by increasing their content of 4,4-dimethylsterols but not of free cholesterol . The ovarian 4,4-dimethylsterol response was followed with regard to time and dose-response to the gonadotropins and the resumption of meiosis was ev aluated using histologic sections. All 4,4-dimethylsterols accumulated in a time-dependent manner in gonadotropin-primed mice after a subsequent stimu lation with hCG. The peak of 4,4-dimethylsterol accumulation appeared postm eiotically but coincided roughly with ovulation, and the resumption of meio sis was triggered when the intraovarian level of MAS was < 20% of its maxim um. The ovarian accumulation of progesterone preceded the 4,4-dimethylstero l accumulation. The FF-MAS accumulation displayed a dose-response maximum w ith respect to hCG, and a variation of the follicular priming regime reveal ed that, in contrast to progesterone production, 4,4-dimethylsterol accumul ation is dependent on previous follicular growth beyond the gonadotropin-de pendent stage. The FF-MAS was not liberated from esterified stores during t he accumulatory response and appeared to be synthesized de novo from a prec ursor (or precursors) metabolically upstream to lanosterol. The data remain inconsistent with a model in which MAS is regarded as the physiological tr igger of meiosis. The 4,4-dimethylsterol accumulation is suggested to influ ence maturation processes by affecting membrane sterol composition.