Bestatin, a potent aminopeptidase-N inhibitor, inhibits in vitro decidualization of human endometrial stromal cells.

Abstract

We have reported that human endometrial stromal cells (ESC) express a cluster of differentiation-13 antigen/aminopeptidase-N, and the expression of this peptidase antigen was shown to increase with the decidualization of ESC. To clarify the role of this peptidase in human endometrium, the effect of bestatin ([(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-(S)-leucine), an inhibitor of aminopeptidase-N, on the decidualization of ESC in vitro was examined. Purified human ESC were cultured for 12 days in the presence of 10(-6) mol/L progesterone with or without bestatin. Decidualization was assessed by PRL production and morphological transformation. The effects of a stereoisomer of bestatin and of pepstatin were similarly examined using the same culture system. Bestatin inhibited progesterone-induced PRL production in a dose-dependent manner, with no effect on cell number or viability, whereas neither its stereoisomer nor pepstatin inhibited aminopeptidase activity or PRL production. The morphological transformation of ESC was also inhibited by bestatin, but not by its stereoisomer or pepstatin. These findings demonstrate that the inhibition of aminopeptidase-N activity blocks the in vitro decidualization of ESC and suggest an important role for this peptidase in the functional differentiation of human ESC.