Ubuka Takayoshi, Tsutsui Kazuyoshi
Department of Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku, Tokyo 162-8480, Japan; Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, 2-8-30 Kounodai, Ichikawa, Chiba 272-0827, Japan.
Department of Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku, Tokyo 162-8480, Japan.
Gen Comp Endocrinol. 2014 Sep 1;205:49-54. doi: 10.1016/j.ygcen.2014.03.014. Epub 2014 Apr 1.
The action of testosterone on male socio-sexual behaviors, such as aggressive and sexual behaviors, requires its aromatization into estrogen (neuroestrogen) in the brain. Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion from the pituitary. On the other hand, wide distribution of GnIH-immunoreactive (ir) neuronal fibers in the brain suggested their roles in the regulation of behavior. Our recent studies have shown that GnIH indeed inhibits aggressive and sexual behaviors. Accordingly, we further investigated the effect of GnIH on aromatase activity and estrogen synthesis in the brain. Abundant GnIH-ir neuronal fibers were observed in the vicinity of aromatase-ir cells in the brain, such as in the preoptic area (POA) that is thought to be the most critical site of aromatization and neuroestrogen action for the regulation of socio-sexual behavior. GnIH receptor (GPR147) mRNA was also expressed in aromatase-ir cells in the POA. GnIH stimulated the activity of aromatase and increased neuroestrogen synthesis in the POA through GPR147. The increase in neuroestrogen concentration in the POA was associated with a significant decrease in aggressive behavior. Finally, centrally administered 17β-estradiol at higher doses inhibited aggressive behavior. These findings indicated that GnIH inhibits aggressive behavior by directly activating aromatase and increasing neuroestrogen synthesis in the brain beyond its optimum concentration for the expression of aggressive behavior. This review highlights recent findings of the role of GnIH in the regulation of neuroestrogen synthesis and its possible function in the regulation of socio-sexual behaviors.
睾酮对雄性社会性行为（如攻击性行为和性行为）的作用，需要其在大脑中芳香化转化为雌激素（神经雌激素）。促性腺激素抑制激素（GnIH）是一种下丘脑神经肽，可抑制垂体促性腺激素的分泌。另一方面，GnIH免疫反应性（ir）神经纤维在大脑中的广泛分布表明它们在行为调节中发挥作用。我们最近的研究表明，GnIH确实会抑制攻击性行为和性行为。因此，我们进一步研究了GnIH对大脑中芳香化酶活性和雌激素合成的影响。在大脑中芳香化酶ir细胞附近观察到大量GnIH-ir神经纤维，如在视前区（POA），该区域被认为是社会性行为调节中芳香化和神经雌激素作用的最关键部位。GnIH受体（GPR147）mRNA也在POA的芳香化酶ir细胞中表达。GnIH通过GPR147刺激POA中芳香化酶的活性并增加神经雌激素的合成。POA中神经雌激素浓度的增加与攻击性行为的显著减少相关。最后，中枢给予高剂量的17β-雌二醇可抑制攻击性行为。这些发现表明，GnIH通过直接激活芳香化酶并增加大脑中神经雌激素的合成，使其超过攻击性行为表达的最佳浓度，从而抑制攻击性行为。本综述重点介绍了GnIH在神经雌激素合成调节中的作用及其在社会性行为调节中可能的功能的最新研究结果。
