The negative and positive feedback actions of estrogen and progesterone on the hypothalamus may be mediated in part by the endogenous opiate system. Estrogen and progesterone suppress physiological responses to the administration of opiate peptides. To determine whether this desensitization to opiates involves receptor down-regulation, we measured the density of naloxone-binding sites in hypothalamic regions regulating gonadotropin release and/or sexual behavior. Using auto radiographic techniques, we measured the density of naloxone- binding sites at various times of the day in intact proestrous, ovariectomized, or ovariectomized rats treated with estrogen or estrogen plus progesterone. Ovariectomy increased naloxone- binding sites compared to intact proestrous rats in all hypothalamic regions examined. Treatment with estrogen decreased and treatment with estrogen plus progesterone decreased even more the densities of naloxone-binding sites. This steroid induced suppression of opiate receptors appears to have important physiological repercussions and provides a basis for the steroid-induced differential sensitivity to exogenous opiates that has been observed previously.
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