TRPM8 as the rapid testosterone signaling receptor: Implications in the regulation of dimorphic sexual and social behaviors

A Mohandass, V Krishnan, ED Gribkova… - The FASEB …, 2020 - Wiley Online Library
A Mohandass, V Krishnan, ED Gribkova, S Asuthkar, P Baskaran, Y Nersesyan, Z Hussain
The FASEB Journal, 2020Wiley Online Library
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 …
Abstract
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.
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