EC 3.4.24.15 is a Putative Regulator of Kisspeptin Signaling

Inadequate kisspeptin (Kiss) secretion or signaling results in delayed puberty and infertility, indicating the importance of this peptide in controlling reproduction. Regulating Kiss, or peptide concentrations in general, are modulated by enzyme hydrolysis altering their downstream signal. The metalloendopeptidase EC 3.4.24.15 (EP24.15) has been demonstrated to play the key role in the cleavage and subsequent regulation of the reproductive hormone Gonadotropin Releasing Hormone (GnRH) in vitro and in vivo that is downstream of Kiss. The goal of these studies borne from structural analyses and in silico molecular modeling was to determine if Kiss is a substrate of EP24.15 by first identifying the cleavage site and enzyme kinetics, and then if EP24.15 and Kiss are co-expressed in brain regions relevant to reproductive function. EP24.15 and Kiss were co-incubated and subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry to confirm that EP24.15 can cleave Kiss in vitro and ...