Abbreviation of the period of sexual behavior in female guinea pigs by the progesterone antagonist RU 486.
In previous studies we have tested the hypothesis that the termination of the period of sexual behavior in female guinea pigs results from the loss of progestin receptors from hypothalamic cell nuclei. We have shown that hormonal manipulations that delay heat termination also delay loss of hypothalamic nuclear progestin receptors. In order to determine if accelerated nuclear receptor loss results in abbreviation of the period of sexual behavior, we tested the effect of 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propyl)-estra-4,9-diene-3-one (RU 486), a progesterone antagonist, on heat termination. Ovariectomized guinea pigs were treated with estradiol benzoate. Forty hours later, they received progesterone followed 4 h later by injection of RU 486 or vehicle. RU 486 injected 4 h after progesterone caused heat abbreviation. We have found that RU 486 administration to estradiol-treated guinea pigs causes accumulation of progestin receptors in cell nuclear extract. Because this accumulation can be detected only when assay conditions are used that promote exchange of RU 486 progestin receptor complexes (15 degrees C incubation rather than 0 degree C); our routine assay conditions (at 0 degree C) can be used to measure primarily receptors that are occupied by progesterone. In order to confirm that RU 486 decreased progesterone-occupied nuclear progestin receptor levels when injected 4 h after progesterone, animals treated as in the behavioral experiment were killed 6 or 10 h after progesterone injection (2 or 6 h after RU 486), and nuclear progestin receptor levels were measured. RU 486 treatment resulted in lowered nuclear concentrations of hypothalamic progestin receptors at both times. These results support our hypothesis that the termination of the period of sexual receptivity in female guinea pigs is the result of loss of progestin receptors from hypothalamic cell nuclei.
D000818:Animals; D002467:Cell Nucleus / Q000032:analysis; D003600:Cytosol / Q000032:analysis; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007031:Hypothalamus / Q000032:analysis*; D007033:Hypothalamus, Middle / Q000032:analysis; D015735:Mifepristone; D010052:Ovariectomy; D011187:Posture; D011301:Preoptic Area / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D004963:Estrenes; D011980:Receptors, Progesterone; D015735:Mifepristone