Interactions between oestradiol and the progesterone antagonist RU-486 in establishing and maintaining female rats' sexual responsiveness: central versus peripheral effects.
Progesterone is well known to contribute specifically to the emergence of the female rats' sexual behaviour by the establishment of 'proceptivity'. Analysis of the mechanism of progesterone action benefits from the availability of highly effective anti-progestagenic compounds. However, results obtained during the study of female rats' sexual behaviour, including such compounds into the experimental protocol, appear equivocal. The present experiments were designed to further examine the possible effects of the antiprogestagenic compound RU-486 (Mifepristone) on the female rats' sexual responsiveness as elicited through exposure of the animals to oestradiol alone. The experimental design aimed to distinguish between receptivity (defined as response to sexually active males) and proceptivity (defined as female-initiated sexual behaviour). Mifepristone advanced the onset of receptivity after the injection of oestradiol benzoate (OB). Upon further investigation a steady level of receptivity was reached during prolonged treatment with OB and this level appeared unaltered through concurrent treatment with Mifepristone. OB alone was insufficient to induce full proceptivity as revealed by observations of sexual behaviour with tethered males. Such defined proceptivity was significantly further inhibited by Mifepristone. It thus appears that, dependent upon the time and type of female sexual behavioural analysis, Mifepristone either enhances, inhibits, or does not affect sexual responsiveness. After the observation period, autopsy revealed the presence of copulatory plugs and infections in the uterus of OB + Mifepristone-treated rats. This unexpected finding could result from effects of the compound on the uterine cervical musculature. Uterine infections might result in painful, aversive, intra-abdominal sensations, especially during intravaginal penile intromissions.(ABSTRACT TRUNCATED AT 250 WORDS)
van der Schoot
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P
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
Baumgarten
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R
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015735:Mifepristone / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000294:innervation
D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol