The generation and metabolism of bioactive peptides involves a series of hi
ghly ordered proteolytic events. This post-translational processing can occ
ur either within the cell, at the cell surface or after secretion. In the c
entral nervous system a number of extracellular peptidases have been implic
ated in the regulated processing of peptides, particularly in the regulatio
n of neuroendocrine function. The aim of this study has been to identify th
e peptidases involved in the metabolism of gonadotropin-releasing hormone (
GnRH) and to characterize the factors and the mechanisms by which the activ
ity of these peptidases are regulated. We have shown that both prolylendo-p
eptidase and the thimet oligopeptidase EC 3.4.24.15 are involved in GnRH me
tabolism and that both oestrogen and thiol-based reductants could be involv
ed in the physiological regulation of their activities.