Mitsushima D, Shinohara K, Kimura F
Department of Neuroendocrinology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama 236-0004, Japan.
Neuroscience. 2004;127(1):243-50. doi: 10.1016/j.neuroscience.2004.04.056.
We showed marked sex differences in the GABA outflow in the medial preoptic area of intact rats. To further determine the sexually dimorphic effects of estrogen on the GABA outflow, an in vivo microdialysis study was performed in gonadectomized rats 3-5 days after the estrogen- or cholesterol-priming. Dialysates and sequential blood samples (150 microl each) were simultaneously collected under freely moving conditions. Serum estradiol concentrations at 72 and 84 h after the estrogen capsule implantation were approximately 75 pg/ml in both sexes. Ovariectomized estrogen-primed (OVX+E(2)) rats showed high GABA outflow from the late night through the morning, which was significantly declined until the onset of surge like secretion of luteinizing hormone (LH) in the afternoon (N=7). Ovariectomized cholesterol-primed (OVX+C) rats consistently showed low GABA outflow and high serum LH concentration (N=8). Conversely, orchidectomized estrogen-primed (ORX+E(2)) rats showed high and episodic GABA outflow without any daily changes (N=7), which was significantly greater than orchidectomized cholesterol-primed (ORX+C; N=8) and OVX+C rats. Only OVX+E(2) rats showed significant daily changes in the GABA outflow and serum LH concentration. Fitting with the double cosinor method demonstrated that the acrophase of the GABA outflow in OVX+E(2) rats occurs in the early morning, whereas the acrophases in OVX+C, ORX+C, and ORX+E(2) rats occur at various times of day. The present findings suggest that sex-specific effects of estrogen on the daily GABA release in the medial preoptic area may be involved in the sex difference of LH release in rats.
我们发现，完整大鼠内侧视前区的γ-氨基丁酸（GABA）释放存在显著的性别差异。为了进一步确定雌激素对GABA释放的性别差异影响，我们对去势大鼠进行了体内微透析研究，这些大鼠在接受雌激素或胆固醇预处理3 - 5天后进行实验。在自由活动条件下，同时收集透析液和连续血样（各150微升）。雌激素胶囊植入后72和84小时，雌雄两性的血清雌二醇浓度均约为75皮克/毫升。卵巢切除并经雌激素预处理（OVX + E₂）的大鼠，从深夜到清晨GABA释放量较高，在下午促黄体生成素（LH）分泌出现类似高峰之前，GABA释放量显著下降（N = 7）。卵巢切除并经胆固醇预处理（OVX + C）的大鼠，GABA释放量持续较低，血清LH浓度较高（N = 8）。相反，睾丸切除并经雌激素预处理（ORX + E₂）的大鼠，GABA释放量高且呈间歇性，无每日变化（N = 7），显著高于睾丸切除并经胆固醇预处理（ORX + C；N = 8）的大鼠和OVX + C大鼠。只有OVX + E₂大鼠的GABA释放量和血清LH浓度有显著的每日变化。用双余弦法拟合表明，OVX + E₂大鼠GABA释放的峰值相位出现在清晨，而OVX + C、ORX + C和ORX + E₂大鼠的峰值相位出现在一天中的不同时间。目前的研究结果表明，雌激素对内侧视前区每日GABA释放的性别特异性影响可能与大鼠LH释放的性别差异有关。
