College of Health Sciences, School of Pharmacy, University of Wyoming, Laramie, WY, USA.
Department of Molecular and Integrative Physiology, Neuroscience Program and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana Champaign, Urbana, IL, USA.
FASEB J. 2020 Aug;34(8):10887-10906. doi: 10.1096/fj.202000794R. Epub 2020 Jul 1.
Testosterone regulates dimorphic sexual behaviors in all vertebrates. However, the molecular mechanism underlying these behaviors remains unclear. Here, we report that a newly identified rapid testosterone signaling receptor, Transient Receptor Potential Melastatin 8 (TRPM8), regulates dimorphic sexual and social behaviors in mice. We found that, along with higher steroid levels in the circulation, TRPM8 male mice exhibit increased mounting frequency indiscriminate of sex, delayed sexual satiety, and increased aggression compared to wild-type controls, while TRPM8 females display an increased olfaction-exploratory behavior. Furthermore, neuronal responses to acute testosterone application onto the amygdala were attenuated in TRPM8 males but remained unchanged in females. Moreover, activation of dopaminergic neurons in the ventral tegmental area following mating was impaired in TRPM8 males. Together, these results demonstrate that TRPM8 regulates dimorphic sexual and social behaviors, and potentially constitutes a signalosome for mediation of sex-reward mechanism in males. Thus, deficiency of TRPM8 might lead to a delayed sexual satiety phenomenon.
睾丸激素调节所有脊椎动物的二态性行为。然而，这些行为背后的分子机制仍不清楚。在这里，我们报告了一种新鉴定的快速睾丸激素信号受体，瞬时受体电位 Melastatin 8（TRPM8），它调节了小鼠的二态性行为和社交行为。我们发现，随着循环中类固醇水平的升高，TRPM8 雄性小鼠表现出增加的无性别偏好的交配频率、延迟的性满足和增加的攻击性，而 TRPM8 雌性小鼠则表现出增加的嗅觉探索行为。此外，急性睾丸激素应用于杏仁核时，TRPM8 雄性小鼠的神经元反应减弱，但雌性小鼠的反应不变。此外，交配后腹侧被盖区多巴胺神经元的激活在 TRPM8 雄性小鼠中受损。总之，这些结果表明 TRPM8 调节二态性行为和社交行为，并且可能构成介导雄性性奖励机制的信号体。因此，TRPM8 的缺乏可能导致性满足延迟现象。
