Physiology of meiosis-activating sterol: endogenous formation and mode of action.
BACKGROUND
In the context of mammalian oocyte maturation, it has been suggested that intermediates of cholesterol biosynthesis may represent the physiological signal that instructs the oocyte to reinitiate meiosis.


METHODS
Endogenous levels of follicular fluid meiosis-activating sterol (FF-MAS) were monitored in rabbit ovarian tissue, and the influence of exogenous gonadotrophins on sterol formation was assessed. The involvement of cAMP in FF-MAS-induced versus spontaneous oocyte maturation in vitro in mice was also investigated, as was the direct microinjection of FF-MAS into mouse oocytes.


RESULTS
Levels of FF-MAS in rabbit ovaries were significantly elevated 1 h after hCG/LH induction and remained so for 4 and 12 h after induction. In naked oocytes undergoing spontaneous maturation, a significant decrease in cAMP was detected after 30 min of culture. However, FF-MAS-mediated induction of oocyte maturation in hypoxanthine-arrested naked oocytes was not associated with any detectable decrease in intracellular cAMP levels. Microinjected FF-MAS failed to induce any noticeable meiosis.


CONCLUSIONS
A rapid increase in FF-MAS level occurred in vivo in the rabbit ovary in response to LH, and clear differences were seen in the cAMP pattern during spontaneous and induced oocyte maturation in mice.
Grøndahl
Christian
C
Fertility Team, Research and Development, Novo Nordisk A/S, Copenhagen, Schering AG, Berlin, Germany. chgr@novonordisk.com
Breinholt
Jens
J
Wahl
Philip
P
Murray
Anthony
A
Hansen
Thomas Høst
TH
Faerge
Inger
I
Stidsen
Carsten E
CE
Raun
Kirsten
K
Hegele-Hartung
Christa
C
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D002782:Cholestenes / Q000008:administration & dosage / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D008845:Microinjections; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000378:metabolism; D011817:Rabbits; D012709:Serum Albumin / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction
D002782:Cholestenes; D006063:Chorionic Gonadotropin; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D019271:Hypoxanthine; C100324:4,4-dimethylcholesta-8,14,24-trienol; D007986:Luteinizing Hormone; D000242:Cyclic AMP