Gonadectomy influences the inhibitory effect of the endogenous opiate system on pulsatile gonadotropin secretion

These studies were designed to evaluate the importance of the gonads on the inhibitory influence exerted by the endogenous opiate system on gonadotropin secretion. The effect of the opioid receptor antagonist naloxone on pulsatile LH secretion was evaluated in 1-, 2-, and 8-week orchidectomized (ORDX) rats. Freely moving rats bearing a Silastic cannula in the right jugular vein were bled every 6 min for 3 h. Saline was injected during the first 90 min, while during the last 90 min naloxone was given as an initial iv bolus injection dose of 2 mg/kg, followed by injections of 0.1 mg/kg every 6 min. In addition, another group of rats was treated, from the beginning of the 3-h bleeding period, with naloxone at an initial iv dose of 2 mg/kg, followed by injections of 0.1 mg/kg every 6 min. Analysis of pulsatile LH secretion showed enhanced mean LH levels, peak and trough values, and pulse duration in 1- and 2-week ORDX rats during the first 40 min of naloxone administration. These changes were essentially restricted to the first pulse that occurred immediately after naloxone administration. No changes in any of the parameters evaluated were observed in 8-week ORDX rats. Different regimens of testosterone replacement (capsules or sc injections) in 8-week ORDX rats significantly reduced the elevated LH value and completely suppressed pulsatile LH secretion. However, in these animals the response of LH to naloxone administration was restored in a limited number of animals among those receiving sc injections. The results indicate that the gonads play a permissive role in the inhibitory action of the endogenous opiate system on gonadotropin secretion, since a loss of sensitivity to opiate receptor blockade takes place after long term gonadectomy. The delayed loss of the response to naloxone after gonadectomy suggests that gonadal factors may have an activational and/or organizational effect on the opiate neurons involved in gonadotropin regulation. The precise mechanism(s) responsible for this loss of sensitivity is still unknown.