Progesterone-induced LHRH release in vitro is an estrogen--as well as Ca++- and calmodulin-dependent secretory process.
Mediobasal hypothalamic (MBH) slices of adult ovariectomized (OVX) rats with or without 17 beta-estradiol (E2) pretreatment, were superfused in buffered (pH 7.2) oxygenated Locke medium containing bacitracin. Pulsatile or continuous administration of progesterone (10(-7) or 10(-8) M) produced a marked increase in luteinizing hormone-releasing hormone (LHRH) release provided the animals had received E2 prior to sacrifice. Omission of Ca++ in the medium, or addition of a Ca++ channel blocker (D-600, 10(-4) M), of a calmodulin inhibitor (trifluoperazine, 30 microM) or of a calmodulin-dependent tubulin kinase inhibitor (phenytoin, 50 microM), antagonized the stimulatory effect of progesterone. When sodium channels were blocked by tetrodotoxin (5 X 10(-7) M), the stimulatory effect of the steroid was completely abolished. The amplitude of the K+-induced LHRH release was slightly increased in the presence of progesterone (10(-7) M) but only from MBH slices of OVX-E2-treated rats. These results indicate that the secretory response of LHRH to progesterone requires priming with estradiol, is Ca++-dependent and involves mediation of calmodulin and a calmodulin-dependent kinase system.
Drouva
S V
SV
Laplante
E
E
Kordon
C
C
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002369:Castration; D046508:Culture Techniques; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007473:Ion Channels; D014268:Trifluoperazine; D007987:Gonadotropin-Releasing Hormone; D013779:Tetrodotoxin; D011374:Progesterone; D004958:Estradiol; D010672:Phenytoin; D002118:Calcium