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首页> 外文期刊>Neuroendocrinology: International Journal for Basic and Clinical Studies on Neuroendocrine Relationships >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.
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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.

机译:AMPA受体调节促性腺激素释放激素和促黄体激素分泌。 AMPA受体在类固醇诱导的促黄体激素激增中的生理作用的证据。

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摘要

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-propionic 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.
机译:近期的研究表明,谷氨酸是雌性动物中促性腺激素释放激素(GnRH)和黄体生成激素(LH)分泌调节的主要递质,尽管尚未完全阐明介导其作用的特定受体和机制。因此,本研究的目的是检验AMPA(α-氨基-3-羟基-5-甲基异恶唑-4-丙酸)型谷氨酸受体在控制雌性动物GnRH和LH分泌中的作用。 。为此,使用体内外方法研究了AMPA对雌性大鼠GnRH和LH分泌的剂量依赖性和类固醇依赖性作用,并且AMPA受体在类固醇诱导的LH激增产生中的作用是还进行了评估。研究结果表明,AMPA的中央给药可刺激雌激素启动的去卵巢成年大鼠的LH释放。还发现AMPA在体外刺激从雌激素引发的去卵巢的成年大鼠的中基底下丘脑(MBH)片段中有效刺激GnRH释放,这种作用被选择性AMPA受体拮抗剂NBQX阻断。 AMPA的作用机制似乎不同于N-甲基-D-天冬氨酸(NMDA),因为AMPA与NMDA相反,未能提高下丘脑的一氧化氮合酶活性。事实证明,AMPA对LH分泌的作用是类固醇依赖性的,因为AMPA的中央给药可刺激雌激素致卵巢切除大鼠的LH释放,但对非雌激素致卵巢切除大鼠的LH释放具有抑制作用。相比之下,AMPA刺激的GnRH从雌激素引发或非雌激素引发的去卵巢大鼠的MBH片段中释放得同样好。 AMPA对LH释放的不同影响可能是由于两个模型之间的垂体敏感性不同,或者,AMPA可以在没有雌激素的情况下刺激去卵巢大鼠中LH抑制因子的释放。最后,建议将AMPA受体在类固醇诱导的LH激增中产生生理作用,这是基于以下发现:将选择性AMPA受体拮抗剂NBQX集中施用至第三脑室可显着减弱类固醇诱导的LH激增。去卵巢的成年雌性大鼠。

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