Hohmann John G, Krasnow Stephanie M, Teklemichael Dawit N, Clifton Donald K, Wynick David, Steiner Robert A
Neurobiology and Behavior Program, University of Washington, Seattle, 98195-7290, USA.
Neuroendocrinology. 2003 Jun;77(6):354-66. doi: 10.1159/000071308.
The peptide galanin has been implicated in the neuroendocrine regulation of reproduction and energy balance. To gain more insight into the functional significance of galanin in these processes, we studied the phenotype of mice that either overexpress galanin in the brain under the control of the dopamine beta-hydroxylase promoter (GALTG) or have a complete absence of galanin expression (GALKO). Both GALTGs and GALKOs had body weights and feeding patterns that were indistinguishable from wild-type (WT) control animals, and both genotypes were reproductively competent. Serum levels of follicle-stimulating hormone were significantly higher in GALKOs and slightly lower in GALTGs than in their respective WT controls. Both GALTGs and GALKOs showed a normal response to fasting, but when GALKO mice were treated with leptin during fasting, levels of corticosterone and testosterone were altered compared to WT mice. In addition, GALKOs were more sensitive than WT controls to the effects of chronic leptin treatment on body weight and fat pad mass, whereas GALTGs showed responses to this metabolic challenge that were indistinguishable from their controls. When galanin was administered centrally, GALKOs had lower testosterone and corticosterone levels than did WT mice. These results suggest that the complete loss of galanin leads to significant alterations in neuroendocrine homeostasis, whereas targeted overexpression of galanin in the brain does not interfere with normal neuroendocrine function.
甘丙肽已被证明参与生殖和能量平衡的神经内分泌调节。为了更深入了解甘丙肽在这些过程中的功能意义，我们研究了在多巴胺β-羟化酶启动子控制下脑内过表达甘丙肽的小鼠（GALTG）或完全缺乏甘丙肽表达的小鼠（GALKO）的表型。GALTG小鼠和GALKO小鼠的体重和进食模式与野生型（WT）对照动物没有区别，且两种基因型均具有生殖能力。GALKO小鼠血清促卵泡激素水平显著高于其WT对照，而GALTG小鼠血清促卵泡激素水平略低于其WT对照。GALTG小鼠和GALKO小鼠对禁食均表现出正常反应，但在禁食期间给GALKO小鼠注射瘦素时，与WT小鼠相比，其皮质酮和睾酮水平发生了改变。此外，GALKO小鼠比WT对照对慢性瘦素治疗对体重和脂肪垫质量的影响更敏感，而GALTG小鼠对这种代谢挑战的反应与对照无差异。向脑内注射甘丙肽时，GALKO小鼠的睾酮和皮质酮水平低于WT小鼠。这些结果表明，甘丙肽的完全缺失会导致神经内分泌稳态的显著改变，而脑内靶向过表达甘丙肽不会干扰正常的神经内分泌功能。
