The physiological role of N-methyl-D-aspartate (NMD A) receptors in the regulation of preovulatory and steroid- induced surges of gonadotropins in the female rat was examined. The specific and potent noncompetitive NMDA receptor antagonist MK801 was used for blockade of NMDA neurotransmission. MK801 treatment completely inhibited the ability of progesterone to induce LH and FSH surges in the estrogen-primed ovariectomized rat. Administration of MK801 on proestrus in the immature female rat primed with PMSG resulted in a significant attenuation of the proestrous LH, FSH, and PRL surge and a corresponding attenuation of ovulation. Similarly, in the adult cycling female rat, MK801 administration on proestrus led to a significant attenuation of the proestrous LH and PRL surges. Mean FSH levels were lower in MK801-treated adult rats than in vehicle-treated rats, but this effect was not significant. In the estrogen-primed ovariectomized immature rat, the agonist NMDA caused a rapid (<10 min) elevation of LH and FSH in vivo. The gonadotropin-releasing effect of NMDA may be mediated at the level of the hypothalamus, since the medial basal hypothalamus/preoptic area of NMDA-treated rats killed 3 and 5 min post-NMDA had a significantly greater release of GnRH in vitro than that of vehicle-treated rats. In conclusion, these findings demonstrate that the preovulatory gonadotropin surge in the female rat is dependent on NMDA neurotransmission for its expression and add further evidence for a critically important role for NMDA receptors in the physiological regulation of gonadotropin secretion in the female rat.
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