BESTATIN, A POTENT AMINOPEPTIDASE-N INHIBITOR, INHIBITS IN-VITRO DECIDUALIZATION OF HUMAN ENDOMETRIAL STROMAL CELLS

We have reported that human endometrial stromal cells (ESC) express a cluster of differentiation-13 antigen/aminopeptidase-N, and the expres sion of this peptidase antigen was shown to increase with the decidual ization of ESC. To clarify the role of this peptidase in human endomet rium, the effect of;bestatin -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 day s in the presence of 10(-6) mol/L progesterone with or without bestati n. Decidualization was assessed by PRL production and morphological tr ansformation. The effects of a stereoisomer of bestatin and of pepstat in were similarly examined using the same culture system. Bestatin inh ibited progesterone-induced PRL production in a dose-dependent manner, with no effect on cell number or viability, whereas neither its stere oisomer nor pepstatin inhibited aminopeptidase activity or PRL product ion. The morphological transformation of ESC was also inhibited by bes tatin, but not by its stereoisomer or pepstatin. These findings demons trate that the inhibition of aminopeptidase-N activity blocks the in v itro decidualization of ESC and suggest an important role for this pep tidase in the functional differentiation of human ESC.