Kauffman Alexander S, Buenzle Jennifer, Fraley Gregory S, Rissman Emilie F
Department of Biochemistry and Molecular Genetics, University of Virginia, 1229 Jordan Hall, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
Horm Behav. 2005 Aug;48(2):141-51. doi: 10.1016/j.yhbeh.2005.01.010. Epub 2005 Mar 19.
Galanin-like peptide (GALP) has been implicated in the neuroendocrine regulation of both feeding and reproduction. In male rodents and primates, intracerebroventricular (icv) infusions of GALP stimulate luteinizing hormone (LH) release, induce Fos expression in brain areas implicated in feeding and reproduction, and affect food intake and body weight in rodents. In gonad-intact and castrated male rats, icv administration of GALP also stimulates male sexual behavior. While the effects of GALP on male physiology and behavior are well documented, no studies have addressed such a role of GALP in females. We tested the effects of icv GALP infusions on LH release, locomotor activity, motor control, and body weight regulation in adult ovariectomized female mice hormonally primed with estradiol benzoate and progesterone. In addition, sexually-experienced male and female mice were treated with GALP and tested for sexual behavior. In females, GALP reduced open-field locomotor activity, the ability to maintain grip on an accelerating rotarod, and 24-h body weight in a dose-dependent manner. GALP also increased LH secretion in female mice, an effect that was blocked by pre-treatment with Antide, a gonadotropin-releasing hormone (GnRH) type-1 receptor antagonist. GALP infusions slightly decreased the occurrence of lordosis behavior in female mice and significantly increased the latencies with which females displayed receptivity. Unlike previous reports in male rats, GALP inhibited male sexual behavior in mice. Our data indicate that in female mice, GALP stimulates LH release via GnRH, and decreases body weight, motor control, and locomotor activity via GnRH-independent pathways. Furthermore, our sexual behavior and locomotor findings suggest species-specific differences in the mechanism and/or location of GALP action in the brains of rats and mice.
甘丙肽样肽(GALP)已被证明参与进食和生殖的神经内分泌调节。在雄性啮齿动物和灵长类动物中,脑室内(icv)注入GALP可刺激促黄体生成素(LH)释放,诱导与进食和生殖相关脑区的Fos表达,并影响啮齿动物的食物摄入量和体重。在性腺完整和去势的雄性大鼠中,icv给予GALP也可刺激雄性性行为。虽然GALP对雄性生理和行为的影响已有充分记录,但尚无研究探讨GALP在雌性中的此类作用。我们测试了icv注入GALP对成年去卵巢雌性小鼠的LH释放、运动活性、运动控制和体重调节的影响,这些小鼠用苯甲酸雌二醇和孕酮进行了激素预处理。此外,对有性经验的雄性和雌性小鼠给予GALP并测试其性行为。在雌性小鼠中,GALP以剂量依赖的方式降低旷场运动活性、在加速旋转杆上保持抓握的能力以及24小时体重。GALP还增加雌性小鼠的LH分泌,该作用被促性腺激素释放激素(GnRH)1型受体拮抗剂Antide预处理所阻断。GALP注入略微降低了雌性小鼠脊柱前凸行为的发生率,并显著增加了雌性小鼠表现出接受性的潜伏期。与先前关于雄性大鼠的报道不同,GALP抑制小鼠的雄性性行为。我们的数据表明,在雌性小鼠中,GALP通过GnRH刺激LH释放,并通过GnRH非依赖途径降低体重、运动控制和运动活性。此外,我们的性行为和运动研究结果表明,GALP在大鼠和小鼠大脑中的作用机制和/或位置存在物种特异性差异。