“…In turn, NKB may act on KNDy neurons to finely tune (predominantly, stimulate) kisspeptin release, therefore inducing GnRH secretion in an indirect manner. This possibility is, at least partially, supported by a solid body of experimental evidence, including the following observations: i) central senktide injection induces expression of C-fos in ARC KNDy neurons (34); ii) senktide elicits LH secretion in a GnRH-dependent manner (28); iii) the LH-releasing effects of senktide are not detected in the absence of proper Gpr54 signaling (35); iv) desensitization to the effects of continuous NKB stimulation takes place at a level upstream of GnRH neurons (28); v) substantial NK3R expression is detected in KNDy, but not GnRH neurons, in rodents and sheep (23); and vi) senktide induces the electrical activation of Kiss1 neurons, as revealed by electrophysiological recordings in Kiss1-CreGFP mice (40). To add further refinement to the system, the third partner of the KNDy trio, Dyn, has been long recognized as an inhibitor of gonadotropin secretion, likely via its ability to repress the release of kisspeptins on of GnRH neurons (12).…”