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 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.
Inoue
T
T
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Japan.
Kanzaki
H
H
Imai
K
K
Narukawa
S
S
Higuchi
T
T
Katsuragawa
H
H
Maeda
M
M
Mori
T
T
D000328:Adult; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D018826:CD13 Antigens; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008875:Middle Aged; D010436:Pepstatins / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000096:biosynthesis; D013237:Stereoisomerism
D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D011374:Progesterone; D011388:Prolactin; D000626:Aminopeptidases; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex; C031375:pepstatin