Endogenous opiates and the hypothalamic-pituitary-gonadal axis in male sheep

The effects of morphine and the opiate receptor antagonist, naloxone, on the secretory pattern of luteinizing hormone (LH) were assessed in male sheep. Morphine infusion (250 mg/hr) abruptly stopped LH pulsatile secretion in castrates (wethers) and decreased mean serum LH concentrations by nearly 70 percent. Response of the pituitary to exogenous LH releasing hormone was not affected by morphine suggesting that the effects of morphine on LH secretion were mediated through the hypothalamus. Estradiol-implanted wethers, characterized by a nonpulsatile LH secretory pattern, responded to intravenous injection of naloxone (20, 50 and 200 mg Lv.) with an immediate release (pulse) of L.H. Similarly, LH release was significantly increased following naloxone infusion (200 mg/hr for four hours) in intact rams and wethers implanted with testosterone or estradiol. In contrast, naloxone infusion altered the pattern of LH secretion in wethers but without affecting mean serum LH concentrations. These results support the notion that LH secretion in male-sheep is tonically regulated by endogenous opiates and further suggests that opioid modulation of the hypothalamic-pituitary-LH axis in sheep involves an interaction with the steroid negative feedback system.