Regulation of gonadotropin-releasing hormone and luteinizing hormone secretion by AMPA receptors - Evidence for a physiological role of AMPA receptors in the steroid-induced luteinizing hormone surge
Regulation of gonadotropin-releasing hormone and luteinizing hormone secretion by AMPA receptors - Evidence for a physiological role of AMPA receptors in the steroid-induced luteinizing hormone surge
复制标题
DOI：
10.1159/000127245
复制
发表时间：
1997-10-01
影响因子：
4.1
通讯作者：
Brann, DW
中科院分区：
文献类型：
--
作者：
Ping, L;Mahesh, VB;Brann, DW
近年来的研究表明，谷氨酸是调节雌性动物促性腺激素释放激素（GnRH）和促黄体生成激素（LH）分泌的主要递质，但其受体和作用机制尚未完全阐明。因此，本研究的目的是研究AMPA（α-氨基-3-羟基-5-甲基异恶唑-4-酸）型谷氨酸受体在雌性动物GnRH和LH分泌控制中的作用。为此，AMPA对雌性大鼠GnRH和LH分泌的剂量和类固醇依赖性影响进行了研究，使用体外和体内方法，AMPA受体在类固醇诱导的LH峰的产生中的作用也进行了评估。研究结果表明，AMPA的中枢给药导致雌激素致敏的卵巢切除成年大鼠LH释放的刺激。AMPA也被发现，有力地刺激GnRH释放在体外从mediobasal下丘脑（MBH）片段获得雌激素引发的卵巢切除成年大鼠，这种效果被阻断的选择性AMPA受体拮抗剂，NBQX。AMPA的作用机制似乎与N-甲基-D-天冬氨酸（NMDA）不同，因为AMPA与NMDA相反，不能提高下丘脑中的一氧化氮合酶活性。AMPA对LH分泌的影响被证明是类固醇依赖性的，因为AMPA的中枢给药刺激了雌激素致敏的卵巢切除大鼠的LH释放，但抑制了非雌激素致敏的卵巢切除大鼠的LH释放。与此相反，AMPA刺激GnRH释放同样好从MBH片段获得雌激素或非雌激素引发卵巢切除大鼠。AMPA对LH释放的不同影响可能是由于两种模型之间垂体的敏感性不同，或者AMPA可能在缺乏雌激素的情况下刺激去卵巢大鼠LH抑制因子的释放。最后，基于选择性AMPA受体拮抗剂NBQX在第三脑室的中枢给药显著减弱了切除卵巢的成年雌性大鼠中类固醇诱导的LH峰的发现，提出了AMPA受体在类固醇诱导的LH峰产生中的生理作用。
Recent work has demonstrated that glutamate functions as a major transmitter involved in the regulation of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in female animals, although the specific receptors and mechanisms mediating its effects have not been completely worked out. The purpose of the present study, therefore, was to examine the role of the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-acid)type glutamate receptor in the control of GnRH and LH secretion in female animals. Toward this end, the dose-and steroid-dependent effects of AMPA on GnRH and LH secretion in female rats were investigated using both in vitro and in vivo approaches, and the role of AMPA receptors in the production of the steroid-induced LH surge was also assessed. The results of the study revealed that central administration of AMPA resulted in a stimulation of LH release in the estrogen-primed ovariectomized adult rat. AMPA was also found to potently stimulate GnRH release in vitro from mediobasal hypothalamic (MBH) fragments obtained from estrogen-primed ovariectomized adult rats, and this effect was blocked by the selective AMPA receptor antagonist, NBQX. The mechanism of action of AMPA appeared to differ from that of N-methyl-D-aspartate (NMDA) as AMPA, in contrast to NMDA, failed to elevate nitric oxide synthase activity in the hypothalamus. The effect of AMPA on LH secretion was demonstrated to be steroid dependent, as central administration of AMPA stimulated LH release in estrogen-primed ovariectomized rats, but was inhibitory to LH release in non-estrogen-primed ovariectomized rats. In contrast, AMPA stimulated GnRH release equally well from MBH fragments obtained from estrogen-primed or non-estrogen-primed ovariectomized rats. The different effects of AMPA on LH release may be due to different pituitary sensitivities between the two models, or alternatively, AMPA may stimulate the release of LH inhibitory factors in the ovariectomized rat in the absence of estrogen. Finally, a physiological role for AMPA receptors in the production of the steroid-induced LH surge was suggested, based on the finding that central administration of the selective AMPA receptor antagonist, NBQX, into the third cerebroventricle significantly attenuated the steroid-induced LH surge in the ovariectomized adult female rat.