Role of endogenous opiates in pubertal maturation: opposing actions of naltrexone in prepubertal and late pubertal boys.

Despite the acute enhancement of gonadotropin output that occurs in the presence of opiate blockade in sexually immature rats and adult men, studies thus far have not demonstrated a role for endogenous opioid peptides during pubertal development in the human. We studied 15 normal boys, 5 sexually developed (Tanner stages IV-V) and 10 sexually infantile, before and after chronic (1-month) administration of a selective micromicron-opiate-receptor antagonist (naltrexone). Gonadotropin secretion was assessed by repetitive venous sampling for 24 h to appraise the pulsatile features of LH release as well as by graded serum LH responses to GnRH. Using an objective pulse detection method, we found that 1) in response to naltrexone, pubertal boys had significantly higher LH pulse frequency (P = 0.044), mean LH concentration (P = 0.0325), and area under the LH vs. time curve (P = 0.0325) compared to those in the basal state; and 2) in sexually immature individuals, naltrexone significantly decreased LH pulse frequency (P = 0.014), mean LH concentration (P = 0.049), and absolute LH peak concentration (P = 0.039) compared to those in the basal state. We suggest that the paradoxical inhibitory response to naltrexone in prepubertal boys represents an agonist-like effect of chronic naltrexone administration. This consideration implies that opiate neural pathways are responsive if not highly sensitive to the agonist effect of opiate substances in the prepubertal male. Accordingly, physiological pubertal progression may be accompanied by decreased sensitivity of the hypothalamic gonadostat to the inhibitory effects of opioid peptides.