Jiang H, Haglof S A, Malven P V
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Life Sci. 1997;60(17):1447-56. doi: 10.1016/s0024-3205(97)00096-9.
The neuroendocrine role of endogenous ligands for the excitatory amino acid receptor subtype known as the NMDA receptor was investigated by administering the NMDA receptor antagonist MK-801 to ovariectomized (ovx) and estradiol-treated sheep. Repetitive administration of MK-801 at intravenous (iv) dosages of 0.1 mg/kg to untreated ovx ewes did not affect the episodic profiles of luteinizing hormone (LH) release, but each injection of MK-801 abruptly stimulated release of prolactin (PRL) demonstrating the effectiveness of the dosage. Injection of estradiol-17beta (50 microg/ewe) to ovx ewes produced the expected biphasic LH response; an initial suppression followed by a surge-like LH increase together with an elevated basal secretion of PRL. Injections of MK-801 occurring 9 and 11 h after estradiol-17beta injection rapidly and transiently increased serum LH in a very unexpected response. However, these same MK-801 injections also resulted in decreased serum LH 14-17 h after estradiol-17beta by delaying the onset of the surge-like release of LH. Estradiol-17beta administration itself elevated basal release of PRL to serum concentrations observed after repetitive MK-801, and further injection of MK-801 no longer transiently increased serum PRL as it had done prior to estradiol-17beta treatment. In summary, antagonizing the endogenous excitatory amino acid ligands of the NMDA receptor with MK-801 did not alter either the timing or magnitude of the putative episodic discharges of gonadotropin-releasing hormone (GnRH) which in turn cause the episodic releases of pituitary LH in ovx sheep. Estrogen administration created a transient neuroendocrine environment in which antagonism of these endogenous ligands was stimulatory to abrupt discharge of GnRH and thereby to acute release of LH. Antagonism of NMDA receptors in untreated ovx ewes stimulated release of PRL suggesting that the endogenous NMDA ligands were probably stimulatory to the release of a PRL-inhibiting neurohormone such as dopamine.
通过给去卵巢（ovx）并经雌二醇处理的绵羊注射N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801，研究了内源性配体对兴奋性氨基酸受体亚型（即NMDA受体）的神经内分泌作用。以0.1mg/kg的静脉注射剂量对未处理的ovx母羊重复注射MK-801，并未影响促黄体生成素（LH）释放的发作模式，但每次注射MK-801都会突然刺激催乳素（PRL）释放，证明了该剂量的有效性。给ovx母羊注射雌二醇-17β（50μg/只）产生了预期的双相LH反应；最初的抑制随后是类似激增的LH增加，同时PRL的基础分泌升高。在注射雌二醇-17β后9小时和11小时注射MK-801，以一种非常意外的反应迅速且短暂地增加了血清LH。然而，这些相同的MK-801注射在雌二醇-17β后14 - 17小时也导致血清LH下降，这是通过延迟类似激增的LH释放的开始。雌二醇-17β给药本身将PRL的基础释放提高到重复注射MK-801后观察到的血清浓度，并且进一步注射MK-801不再像在雌二醇-17β治疗之前那样短暂增加血清PRL。总之，用MK-801拮抗NMDA受体的内源性兴奋性氨基酸配体，既没有改变促性腺激素释放激素（GnRH）假定的发作性放电的时间或幅度，而GnRH反过来又会导致ovx绵羊垂体LH的发作性释放。雌激素给药创造了一个短暂的神经内分泌环境，在其中拮抗这些内源性配体对GnRH的突然释放有刺激作用，从而对LH的急性释放有刺激作用。在未处理的ovx母羊中拮抗NMDA受体刺激了PRL的释放，这表明内源性NMDA配体可能对催乳素抑制性神经激素（如多巴胺）的释放有刺激作用。
