Gonadotropin-inhibitory hormone inhibits aggressive behavior of male quail by increasing neuroestrogen synthesis in the brain beyond its optimum concentration

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.