title: The plasma levels of protein Z-dependent protease inhibitor increase after gynecological surgery independently of estrogen.
abstract: BACKGROUND
  Protein Z (PZ)-dependent protease inhibitor (ZPI) is a serine protease inhibitor that efficiently inhibits activated factor X when ZPI is in complex with PZ. We previously reported significantly higher concentrations of plasma ZPI (and PZ) in women during normal pregnancy than in non-pregnant women.
  
  
  METHODS
  We explored the possible contribution of estrogen to the ZPI levels in patients with or without bilateral oophorectomy (OVX), which induces artificial menopause where blood estrogen levels drastically decrease. One hundred ninety-one pre-menopausal Japanese women who underwent open hysterectomy owing to neoplasms participated in this study and were divided into two groups: 98 OVX and 93 Non-OVX cases. Plasma ZPI was measured by ELISA.
  
  
  CONCLUSIONS
  Contrary to our working hypothesis, plasma ZPI levels increased significantly in the OVX group after surgery when compared with the pre-operation levels. When these patients were individually analyzed, their ZPI value also rose significantly from pre-operation to post-operation levels. In contrast, plasma PZ levels remained unchanged. The significantly increased ZPI and unchanged PZ levels were also observed in the Non-OVX group. The increased ZPI levels were not significantly related to 17β-estradiol, luteinizing hormone or follicular stimulating hormone levels, clearly indicating that estrogen did not contribute to the plasma ZPI concentrations. Typical acute phase reactants fibrinogen and C-reactive protein (CRP) were also significantly elevated after surgery in both OVX and Non-OVX groups. However, only weakly significant linear relationships were observed between ZPI and fibrinogen or CRP, indicating the presence of alternative regulatory mechanisms underlying their plasma concentrations.
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Souri
authors.affiliation: Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Osaki
authors.affiliation: Department of Obstetrics and Gynecology, Toyama University, Graduate School of Medical Sciences, Toyama 930-0194, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kurachi
authors.affiliation: Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. Electronic address: aichinos@med.id.yamagata-u.ac.jp.
authors.forename: Akitada
authors.initials: A
authors.lastname: Ichinose
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D004967:Estrogens / Q000378:metabolism*; D013509:Gynecologic Surgical Procedures / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D011480:Protease Inhibitors / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D004967:Estrogens; D011480:Protease Inhibitors
keywords: Acute phase reactant; Cancer; Coagulation inhibitors; Female hormones; Protein Z-dependent protease inhibitor; Surgery