Possible implication of midkine in the development of endometriosis.
BACKGROUND
The present study was conducted to assess whether midkine (MK), a multifunctional molecule known to stimulate tumor growth, may be involved in the development of endometriosis.


METHODS
The mitogenic activity of MK on cultured endometriotic stromal cells was examined by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation. Concentrations of MK in the peritoneal fluid (PF) of women without or with endometriosis and those under GnRH agonist treatment were measured using a specific enzyme immunoassay. The expression of MK mRNA in peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues was evaluated by RT-PCR.


RESULTS
MK significantly increased BrdU incorporation into the DNA of cultured endometriotic stromal cells. The MK concentrations in the PF of the women with advanced endometriosis (stages II, III and IV) Median: 1.21 ng/ml; interquartile range 0.80-2.27 were significantly higher than those of the women without endometriosis and with stage I endometriosis (0.06 ng/ml, 0.67-1.26, P < 0.05). As for the menstrual phase, the MK concentration in PF in the inteal phase (1.32 ng/ml. 0.72-2.21) were significantly higher than those in the follicular phase (0.95 ng/ml, 0.68-1.24, P < 0.05). In addition, women with adnexal adhesions had higher concentrations of MK in PF than those without adhesions (P < 0.05). The MK concentrations of the women under GnRH agonist treatment were significantly lower than those of the other groups (P < 0.001). The expression of MK mRNA was detected in peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues.


CONCLUSIONS
The present findings suggest that MK may play roles, such as stimulation of endometriotic cell proliferation, in the development of endometriosis.
Hirota
Yasushi
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo, 113-8655, Japan.
Osuga
Yutaka
Y
Koga
Kaori
K
Yoshino
Osamu
O
Hirata
Tetsuya
T
Harada
Miyuki
M
Morimoto
Chieko
C
Yano
Tetsu
T
Tsutsumi
Osamu
O
Sakuma
Sadatoshi
S
Muramatsu
Takashi
T
Taketani
Yuji
Y
D000328:Adult; D001202:Ascitic Fluid / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004717:Endometrium / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D000078792:Midkine; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000502:physiology
D016207:Cytokines; D012333:RNA, Messenger; D000078792:Midkine