Ontogeny of the opioid-mediated control of reproductive endocrinology in the male and female rat

Endogenous opioids (EOP) appear to inhibit the release of luteinizing hormone-releasing hormone and, subsequently, luteinizing hormone (LH). These observations have led to the hypothesis that EOP-containing neuronal systems may be involved in the onset of puberty. To examine this possibility, rats were challenged with naloxone and morphine, as probes to decrease or exaggerate, respectively, the effects of EOP on luteinizing hormone releasing hormone/LH release at intervals from birth to adulthood. Morphine had no effect on serum LH up to 15 days of age in males, but thereafter was maximally effective. On the other hand, the onset of adult-appropriate responses to morphine occurred much later in females (30-35 days) and the depressions in LH were consistently less pronounced than in comparably aged males. Naloxone produced large increases in LH in 10- and 25-day-old females, but was ineffective at 15 or 20 days. After day 25, the response to naloxone declined gradually, but was still significantly greater than control values in adults. In contrast, naloxone failed to increase serum LH from 10 to 30 days after birth in males. Beginning at 30 to 35 days of age, however, a sudden onset in the sensitivity to naloxone occurred which increased exponentially until 60 days. At this time, serum LH levels were 5 times greater in naloxone-treated males than in controls, and were twice those found in similarly treated females. These age-and sex-related differences in response to the opiates were not related to pharmacokinetic variables and also could not be attributed to gross maturational alterations in the hypothalamic-pituitary-gonadal axis. Thus, our results seem to reflect inherent ontogenetic differences in the EOP-mediated regulation of luteinizing hormone-releasing hormone/LH which may be related to the onset of puberty and sexual maturation.