N-methyl-D-aspartic acid receptor messenger ribonucleic acid levels and luteinizing hormone release in immature female rats: effects of stage of pubertal development and exposure to ethanol.

This research was designed to determine 1) whether changes occur in the levels of N-methyl-D-aspartic acid (NMDA) receptor (NMDA-R) messenger RNA (mRNA) in the reproductive hypothalamus of female rats as they approach puberty, 2) whether NMDA-R stimulation would promote differential LH responses during the specific stages of peripubertal development, and 3) whether ethanol (ETOH), which is known to affect the NMDA-R in other brain systems, can alter NMDA-R-activated LH secretion at puberty. In the first experiment, female rats were killed at 15, 20, 25, and 34-36 days of age to determine the levels of mRNA that code for the NMDA-R, specifically NMDA-R1, in the arcuate nucleus-median eminence (AN-ME) and preoptic area (POA) during pre- and peripubertal development by a ribonuclease protection assay. Results indicate that in juvenile animals, NMDA-R mRNA levels in the AN-ME increased at 25 days (P < 0.01). In the POA, the levels increased at 20 days (P < 0.05), but were unchanged at 25 days. During the peripubertal period, NMDA-R gene expression in the AN-ME did not change; however, gene expression in the POA increased (P < 0.05) during first proestrus, then declined during first estrus. In the second experiment, NMDA-R stimulation with N-methyl-D,L-aspartic acid (NMA; 2.5 mg/kg) produced differential stimulatory effects on LH release depending upon the stage of pubertal development. In this regard, significant post-NMA percent increases in LH released over pre-NMA (basal) levels occurred during anestrus (46%; P < 0.01) and first proestrus (95%; P < 0.01), with nonsignificant increases of 18% and 28% during first estrus and diestrus, respectively. Finally, a 3 g/kg dose of ETOH given intragastrically 90 min before the NMA challenge blocked (P < 0.05) NMA-induced LH release during first proestrus. In conclusion, these findings demonstrate regional differences in the timing of NMDA-R gene expression in the reproductive hypothalamus during pubertal development, show differential responses of LH to NMDA-R activation during the peripubertal period, and continue to demonstrate the vulnerability of the hypothalamic-pituitary axis to the detrimental effects of ETOH at this critical time of development.