Failure of protein synthesis inhibition to block progesterone desensitization of lordosis in female rats.
Progesterone's desensitization effect on lordosis has been shown to correlate with a decreased concentration of hypothalamic progestin receptors after progesterone injection. In a recent study, one group of investigators found that the protein synthesis inhibitor anisomycin appeared to block progesterone's desensitization effect. Despite decreased levels of cytoplasmic progestin receptors, progesterone + anisomycin-treated rats exhibited a high level of lordosis four hr after a second progesterone injection. Because this finding conflicts with a progestin receptor model of progesterone's desensitization effect, we investigated it further. In the first experiments, ovariectomized rats were injected with estradiol benzoate followed 24 hr later by either progesterone or vehicle. Anisomycin injected 3 hr after progesterone, at a dose that causes inhibition of hypothalamic protein synthesis for at least 4 hr, was without effect on progesterone desensitization a day later. In other experiments silastic implants containing estradiol were inserted into ovariectomized rats. Forty-five hr later, rats received progesterone or vehicle, followed by injections of anisomycin or saline. Rats receiving anisomycin + progesterone were still highly receptive at 30 hr while saline + progesterone controls were not. Furthermore, the results were similar 4 hr after a second injection of progesterone at 30 hr. In a related experiment, we confirmed that anisomycin delayed dramatically termination of the period of sexual receptivity. In this laboratory anisomycin does not seem to block progesterone's desensitization effect. However, with certain procedures anisomycin delays the termination of sexual receptivity. Thus it is important in investigations of the mechanism of progesterone's desensitization effect that animals be tested prior to the second progesterone injection to determine if they are actually responding to the progesterone.
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D002369:Castration; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000187:drug effects; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D011759:Pyrrolidines; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D000841:Anisomycin