Characterization of the Action of Tachykinin Signaling on Pulsatile LH Secretion in Male Mice

The alternation of the stimulatory action of the tachykinin neurokinin B (NKB) and the inhibitory action of dynorphin within arcuate (ARH) Kissl neurons has been proposed as the mechanism behind the generation of gonadotropin-releasing hormone (GnRH) pulses through the pulsatile release of kisspeptin. However, we have recently documented that GnRH pulses still exist in gonadectomized mice in the absence of tachykinin signaling. Here, we document an increase in basal frequency and amplitude of luteinizing hormone (LH) pulses in intact male mice deficient in substance P, neurokinin A (NKA) signaling (Tac1KO), and NKB signaling (Tac2KO and Tacr3KO). Moreover, we offer evidence that a single bolus of the NKB receptor agonist senktide to gonad-intact wild-type males increases the basal release of LH without changing its frequency. Altogether, these data support the dispensable role of the individual tachykinin systems in the generation of LH pulses. Moreover, the increased activity of the GnRH pulse generator in intact KO male mice suggests the existence of compensation by additional mechanisms in the generation of kisspeptin/GnRH pulses.

Automated summary

The interaction between NKB and dynorphin within arcuate Kiss1 neurons generates GnRH pulses, but these pulses still exist even in the absence of tachykinin signaling. In mice deficient in substance P, NKA, and NKB signaling, there is an increase in the frequency and amplitude of LH pulses. Administration of an NKB receptor agonist in intact male mice increases basal LH release without affecting its frequency, suggesting the existence of compensatory mechanisms in the generation of kisspeptin/GnRH pulses in these animals.