Advancement of first ovulation by the opioid antagonist naltrexone

The opioid antagonist naltrexone was administered to female rats during the late juvenile period, and its effects on sexual maturation were studied. Naltrexone treatment (2.5 or 20 mg/kg; four daily injections at 2-h intervals) at 28-32 days of age advanced first ovulation in about 55% of the rats. When naltrexone (20 mg/kg) was administered at 30-34 days of age, 75% of the rats responded. In these rats, first ovulation was advanced by 3.4 days and their body weight was 15.1 g lower than in control rats at first ovulation (p less than 0.01). Similar naltrexone treatment at younger (starting on Day 24 or 26) or older (starting on Day 32 or 34) ages did not advance first ovulation. The numbers of ova released in advanced, nonadvanced, and control rats were similar. A significant increase in serum luteinizing hormone (LH) concentration was seen 15 min after naltrexone injection (20 mg/kg) at all ages studied; the increase was significantly higher (p less than 0.05) at 30 days of age than before or after that age. Relatively high response to naltrexone (2.5 mg/kg) was seen from 8 to 4 days before first ovulation. Taken together, these data suggest that during the late juvenile stage (8 - 4 days before first ovulation) endogenous peptides critically restrict LH secretion and may constitute a hypothalamic restraint on the onset of puberty. However, changes in pituitary responsiveness to luteinizing hormone-releasing hormone may be part of the mechanism behind the high LH response to naltrexone in rats during the late juvenile stage.