Participation of TRPV1 in the activity of the GnRH system in male rats

GnRH neuron activity is under the influence of multiple stimuli, including those coming from the endocannabinoid and the immune systems. Since it has been previously suggested that some of the main elements controlling the GnRH pulse generator possess the TRPV1 receptor, the aim of the present study was to evaluate the participation of the hypothalamic TRPV1, through its pharmacological blockade, in the activity of the hypothalamic‐pituitary‐testicular axis in male rats under basal or acute inflammatory conditions. Our hypothesis was based on the idea that the hypothalamic TRPV1 participates in the synthesis of the main neuromodulatory signals controlling GnRH, and therefore the reproductive axis. Our results showed that the hypothalamic TRPV1 blockade induced pro‐inflammatory effects by increasing Tnfα and Il‐1β mRNA hypothalamic levels and inhibited the reproductive axis by affecting Gnrh, Kiss1 and Rfrp3 mRNA levels and decreasing plasma levels of luteinizing hormone and testosterone under basal conditions, without significant additive effects in rats exposed to systemic LPS. Altogether, these results suggest that the hypothalamic TRPV1 receptor participates in the regulation of the GnRH system, probably by modulating immune‐dependent mechanisms. In the hypothalamus, GnRH is under the influence of multiple stimuli such as kisspeptin and Rfrp‐3 signaling. Moreover, GnRH stimulates LH and subsequently testosterone release to the bloodstream. Using an animal in vivo model, we showed that GnRH, kisspeptin and RFRP‐3 mRNA synthesis are influenced by the TRPV1 channel. The influence could be direct if these neurons would express the channel, or could be indirect, mediated by another neuronal population or by the hypothalamic cytokine tone.