Luteinizing hormone sensitivity to naloxone in maturing male chimpanzees

We have systematically investigated the involvement of endogenous opioids in gonadotropin secretion during primate sexual maturation by examining LH/FSH responses to gonadotropin-releasing hormone (GnRH) and changes in LH secretion during infusions of saline or naloxone, an opiate antagonist, in ten male chimpanzees between one and nine years of age. Animals were anesthetized with ketamine (10 mg/kg) and injected or infused IV with GnRH, naloxone or saline. Circulating levels of serum LH were elevated to the same extent (approximately 400%) in response to GnRH (100 micrograms) in animals 1-5 years old (juvenile) and in animals 6-9 years old (pubertal). No differences were noted between the two groups in GnRH-stimulated levels of serum FSH. During treatment with naloxone (0.14 mg/kg bolus followed by 0.2 mg/kg/h maintenance infusion for 3 h), serum LH levels in pubertal animals were significantly (p less than 0.05) elevated by as much as 95% over LH levels found during treatment with saline. Juvenile animals, on the other hand, failed to demonstrate significant increases in serum LH following naloxone at the doses tested. A strong correlation (r = .84) was found between circulating testosterone and serum LH levels during naloxone treatment. These data indicate that opioid inhibition of LH secretion can be reversed by naloxone only when puberty is reached in chimpanzees and suggest an alteration in opioid regulation of GnRH near the time of puberty. The strong correlation between testosterone levels and LH responses to naloxone suggests that steroids may participate in the maturation of opioid control of LH during puberty of nonhuman primates.