Neonatal Melatonin Administration Advances Rat Vaginal Opening and Disrupts Estrous Cyclicity and Estrogen‐Dependent Regulatory Mechanisms of Luteinizing Hormone and Prolactin

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Abstract
Melatonin (100 μrat) was administered to female rats on day 5 of life, 3 hours prior to the onset of darkness or at 12:00 hours. Melatonin administration induced precocious puberty in both cases, as indicated by the advance of the time of the vaginal opening and the appearance of the first estrous smear as compared with controls (P < 0.01), together with an increase in the number of estrous smears (P < 0.05) and a reduction in the number of thestrous smears (P < 0.05). Decreased serum prolactin levels were observed on day 21 of age (P < 0.05) in melatonin‐treated rats with both of the melatonin injection times as compared with controls. No differences were apparent in basal luteinizing hormone (LH) levels either at 30 or at 60 days of age comparing melatonin‐ and vehicle‐treated rats with either of the scheduled melatonin injection times. As to serum follicle‐stimulating levels (FSH) levels, there was a marked decrease in circulating FSH levels in melatonin‐treated rats in both cases on days 21, 30, and 45 (P < 0.05) as compared with controls. A marked increase of serum prolactin at both 48 and 55 hours after estradiol benzoate (EB) administration was detected in 30‐day‐old melatonin‐treated rats as compared with controls (P < 0.05 for both points). Also, an increased responsiveness of prolactin to EB was found on the first day post‐administration. At 60 days of age, an increase in prolactin responses to EB was observed on the first day post‐administration (31 and 48 hours after, (P < 0.01), whereas no differences were detected at any other stuthed time. The LH burst that occurs 31 hours after EB administration in 30‐day‐old rats was decreased in melatonin‐treated animals as compared with controls (P < 0.05). In 60‐day‐old melatonin‐treated rats, a marked increase in the LH response to EB administration, 31 hours after injection (P < 0.01), was observed. These data suggest that neonatal melatonin administration in pharmacological amounts induces precocious puberty as measured by vaginal opening and, furthermore, it advances the appearance of the first estrous smear with age‐dependent modifications of estrous cyclicity and prolactin and LH responses to EB.