Ethanol Alters N-Methyl-<i>DL</i>-Aspartic Acid-Induced Secretion of Luteinizing Hormone Releasing Hormone and the Onset of Puberty in the Female Rat

In the present study, we have evaluated the effects of ethanol (ETOH) on luteinizing hormone releasing hormone (LHRH) secretion induced by N-methyl-DL-aspartic acid (NMA) in vitro and the ability of NMA to induce precocious puberty in vivo. For the in vitro experiments, the basal and NMA-stimulated release of LHRH from arcuate nucleus-median eminence (AN-ME) fragments obtained from immature female rats was measured by RIA following static incubation in medium consisting of Krebs-Ringer bicarbonate glucose buffer. Control vials contained medium only and the test vials contained medium plus ETOH doses of 30, 50, and 70 mM. These data demonstrate that ETOH did not alter basal LHRH release, but dose-dependently blocked (p < 0.01) the NMA-induced release of the peptide during anestrus, as well as first proestrus and estrus. For the in vivo experiment, 26-day-old females began receiving saline or saline-ETOH (3 g/kg) solution by gastric gavage daily at 12.30 p.m. Each day at 2.00 and 4.00 p.m., each of the animals received subcutaneous injections of a 40-mg/kg solution of NMA in saline. Other control animals received saline gastrically, as well as subcutaneously. The timing of puberty was assessed in all animals by monitoring vaginal opening (VO) and first diestrus (D1). The mean (±SEM) age at VO for animals in the non-ETOH group, which received NMA, was 31.7 ± 0.40 days. Vaginal smears revealed that D1 occurred at a mean ( ± SEM) age of 33.0 ± 0.42 days. Thus, puberty was significantly (p < 0.01) advanced when compared to the non-NMA controls, which showed VO at 36.3 ± 0.77 and Di at 37.6 ± 0.74 days. Conversely, the ETOH-treated rats showed VO at 34.2 ± 0.46 and D1 at 35.8 ± 0.37 days, indicating that ETOH significantly (p < 0.01) attenuated the ability of NMA to induce puberty. Therefore, the present results further demonstrate that the activation of the NMD A receptor plays a role in the onset of female puberty, and suggest that ETOH can interfere with the pubertal process via its action at the hypothalamic level to diminish excitatory amino acid-activated LHRH secretion.