Requirement for proprotein convertase 5/6 during decidualization of human endometrial stromal cells in vitro.
Decidualization of endometrial stromal cells (ESCs) is critical for embryo implantation and maintenance of pregnancy. Proprotein convertase (PC) 5/6 is suggested to play an important role in the processes of stromal cell decidualization and embryo implantation in the mouse. PC5/6 is a member of the PC family responsible for processing precursor proteins to their active forms by selective proteolysis. In this study, we investigated the regulation of PC5/6 mRNA and protein expression in human ESCs during decidualization in vitro. Real-time PCR analyses revealed a significant increase in PC5/6 mRNA levels in ESCs treated with 17 beta-estradiol (E(2)) plus medroxy-progesterone acetate during decidualization. On the other hand, E(2) alone did not increase PC5/6 mRNA expression. Intense PC5/6 immunoreactivity was observed in the cytoplasm of E(2) plus medroxy-progesterone acetate-treated ESCs (decidualized ESCs) compared with E(2)-treated ESCs on d 12 of culture (nondecidualized ESCs). This PC5/6 immunoreactivity was abolished by cotreatment with ZK 98299, a progesterone receptor antagonist. Western blotting revealed PC5/6 as approximately 120-kDa bands (pro- and mature forms) and a 65-kDa band (C-terminally truncated form) in decidualized ESCs. Using an antisense morpholino approach, prolactin production, a typical marker for decidualization, was significantly attenuated in decidualized ESCs after treatment with PC5/6 morpholino antisense oligonucleotides in comparison with controls. These results suggest that PC5/6 plays a key role for decidualization in human endometrium.
Okada
Hidetaka
H
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia. hodaka@takii.kmu.ac.jp
Nie
Guiying
G
Salamonsen
Lois A
LA
D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004717:Endometrium / Q000166:cytology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D045702:Proprotein Convertase 5 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology* / Q000502:physiology
D012333:RNA, Messenger; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D045702:Proprotein Convertase 5