Chronic Morphine Treatment Induces Hypersensitivity to Testosterone-negative Feedback in Castrated Male Rats

Studies were undertaken to determine the effects of chronic stimulation of opiate receptors on the negative feedback effects of testosterone (T) on luteinizing hormone (LH) secretion in the male rat. In an initial study, castrated male rats received replacement levels of T (2 ng/ml) or chronic morphine (M) treatment for 7 days. When initiated at the time of castration, both T and M treatments prevented the castration-induced hypersecretion of LH. However, when the treatments commenced 2 weeks after castration, only T restored LH secretion to the low levels seen in intact rats. In a second study, rats castrated 2 weeks previously were exposed to chronic M or placebo (control) treatment in the presence of various dosages of T. In rats receiving T alone, LH secretion was unaffected at T levels up to 600 pg/ml serum, but thereafter there was a dose-dependent suppression of LH release by T. Serum T levels which reduced LH secretion by 50% were estimated to be 966 pg/ml. In contrast, in castrated rats receiving both M and T treatment, a 50% reduction in LH secretion was estimated to be at 300 pg T/ml serum and maximal inhibition of LH secretion was achieved at serum T levels of greater than 600 pg/ml. Neither T alone nor M plus T treatment altered the responsiveness of the anterior pituitary to LHRH in vitro. These findings indicate that M may enhance the sensitivity of the hypothalamus to T feedback by approximately 3-fold and raise the possibility of the existence of an opioid-sensitive neural component which may modulate the negative feedback effects of T on LH secretion.