The effect of naloxone on the negative feedback action of gonadal steroids on luteinizing hormone (LH) release was studied in castrated male and female rats. The reduction by estradiol benzoate or testosterone propionate of elevated serum LH levels in rats ovariectomized for 4 weeks was reversed by a single injection of naloxone. Injection of estradiol benzoate, together with progesterone, similarly reduced serum LH levels in ovariectomized rats, and this inhibition was partially reversed by naloxone. A single injection of testosterone propionate decreased serum LH levels in male rats castrated 48 h earlier, and naloxone completely blocked the androgen-induced inhibition of LH secretion. Chronic administration of either testosterone propionate or morphine sulfate to castrated male rats prevented the postcastration rise of serum LH. The decrease of hypothalamic LHRH in castrated rats was completely blocked by testosterone propionate or morphine sulfate administration. These results are believed to indicate that hypothalamic opiates are involved in gonadal steroid feedback inhibition of LH release.

The purpose of this study was to determine the effects of morphine and naloxone on pulsatile release of LH in ovariectomized rats treated (or untreated) with ovarian steroids. Ovariectomized rats were given a subcutaneous injection of estradiol benzoate (20 µg) or estradiol benzoate (20 µg) and progesterone (10 mg) 3 days prior to experimentation. The rats were then given intravenous injections of naloxone (2 mg/kg), morphine (5 mg/kg), or 0.87% NaCl every hour for 3 h. For LH assays, 0.3 ml blood was collected via an atrial cannula 15 min after drug treatment and every 15 min thereafter for 3 h. Pulsatile LH release was suppressed by estradiol benzoate or the combination of estradiol benzoate and progesterone. Naloxone was able to counteract inhibition of pulsatile LH release by these steroids. These results suggest that the endogenous opioid peptides are involved in the negative feedback exerted by estrogen and progesterone on pulsatile LH release. Morphine had no effect on steroid inhibition of pulsatile LH release.

A single injection of the opiate antagonist, naloxone (NAL), resulted in a fourfold increase in serum luteinizing hormone (LH) concentration 20 min after injection. To determine whether noradrenergic neurons were involved, male Sprague-Dawley rats were treated with α-methyl-p-tyrosine (α-MPT), phenoxybenzamine hydrochloride (PBH), or diethyl-dithiocarbamate (DDC), all anti-noradrenergic drugs. Reduction of hypothalamic norepinephrine synthesis by α-MPT or DDC, or blockade of the α-receptors by PBH, resulted in complete suppression of NAL-induced LH release. These results suggest that the NAL-induced increase in LH release is mediated in part via a hypothalamic noradrenergic mechanism.

No abstract