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-dimethylsterols termed meiosis-activating sterols (MAS). The levels of meiosis active (follicular fluid [FF]-MAS and bull testes [T]-MAS) and inactive (lanosterol) 4,4-dimethylsterols, free cholesterol, and progesterone were determined in gonadotropin-primed prepubertal mouse ovaries in vivo by high-performance 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 evaluated using histologic sections. All 4,4-dimethylsterols accumulated in a time-dependent manner in gonadotropin-primed mice after a subsequent stimulation with hCG. The peak of 4,4-dimethylsterol accumulation appeared postmeiotically but coincided roughly with ovulation, and the resumption of meiosis was triggered when the intraovarian level of MAS was <20% of its maximum. The ovarian accumulation of progesterone preceded the 4,4-dimethylsterol accumulation. The FF-MAS accumulation displayed a dose-response maximum with respect to hCG, and a variation of the follicular priming regime revealed that, in contrast to progesterone production, 4,4-dimethylsterol accumulation is dependent on previous follicular growth beyond the gonadotropin-dependent stage. The FF-MAS was not liberated from esterified stores during the accumulatory response and appeared to be synthesized de novo from a precursor (or precursors) metabolically upstream to lanosterol. The data remain inconsistent with a model in which MAS is regarded as the physiological trigger of meiosis. The 4,4-dimethylsterol accumulation is suggested to influence maturation processes by affecting membrane sterol composition.
Baltsen
M
M
Laboratory of Reproductive Biology, The Rigshospital, DK-2100 Copenhagen Ø, Denmark. mogens.lrb@rh.dk
D000818:Animals; D002775:Cholestadienols / Q000378:metabolism*; D002782:Cholestenes / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004951:Esterification; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D006062:Gonadotropins / Q000494:pharmacology*; D007700:Kinetics; D007810:Lanosterol / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010060:Ovulation; D011374:Progesterone / Q000378:metabolism
D002775:Cholestadienols; D002782:Cholestenes; D006063:Chorionic Gonadotropin; D006062:Gonadotropins; C071868:4,4-dimethylcholesta-8,14-dien-3-ol; D007810:Lanosterol; D011374:Progesterone; C100324:4,4-dimethylcholesta-8,14,24-trienol; D002784:Cholesterol