Brann D W, Mahesh V B
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000.
Endocrinology. 1991 Mar;128(3):1541-7. doi: 10.1210/endo-128-3-1541.
The physiological role of N-methyl-D-aspartate (NMDA) 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 (less than 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.
研究了N-甲基-D-天冬氨酸（NMDA）受体在调节雌性大鼠促排卵及甾体诱导的促性腺激素激增中的生理作用。使用特异性且强效的非竞争性NMDA受体拮抗剂MK801来阻断NMDA神经传递。MK801处理完全抑制了孕酮诱导雌激素预处理的去卵巢大鼠促黄体生成素（LH）和促卵泡生成素（FSH）激增的能力。在经孕马血清促性腺激素（PMSG）预处理的未成熟雌性大鼠动情前期给予MK801，导致动情前期LH、FSH和催乳素（PRL）激增显著减弱，排卵相应减少。同样，在成年发情周期的雌性大鼠中，动情前期给予MK801导致动情前期LH和PRL激增显著减弱。MK801处理的成年大鼠的平均FSH水平低于载体处理的大鼠，但这种效应不显著。在雌激素预处理的未成熟去卵巢大鼠中，激动剂NMDA在体内引起LH和FSH快速（少于10分钟）升高。NMDA的促性腺激素释放作用可能在下丘脑水平介导，因为在给予NMDA后3分钟和5分钟处死的NMDA处理大鼠的内侧基底部下丘脑/视前区，体外GnRH释放显著高于载体处理的大鼠。总之，这些发现表明雌性大鼠排卵前促性腺激素激增的表达依赖于NMDA神经传递，并进一步证明了NMDA受体在雌性大鼠促性腺激素分泌的生理调节中起至关重要的作用。
