Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats.
Polycystic ovary syndrome (PCOS) is characterized by cystogenesis; however, the cause of this cystogenesis is unknown. At ovulation, preovulatory collagenolytic activities in the ovarian follicles increase and various proteinases are needed to degrade the tissues surrounding the follicles. To clarify the roles of enzymes in collagen degradation of the follicular wall of polycystic ovary (PCO) in relation to the cystogenesis, we examined expression of lysyl oxidase (LOX), which initiates cross-link formation of the collagen and elastin in the extracellular matrix, and expression of matrix metalloproteinases (MMPs) in ovaries of model rats with PCO induced by dehydroepiandrosterone (DHEA) compared with MMP expression in control rats. DHEA treatment increased LOX mRNA expression to more than three times the control value (P: < 0.01). MMP-2 mRNA expression in control rats was threefold greater than that in the DHEA-induced group (P: < 0.05). Expression of both latent and active forms of MMP-2 in controls was more than twice that in the DHEA-induced group (P: < 0.05) as shown by Western blotting, and expression of the active form of MMP-2 was also twice as high in the controls as in the DHEA-treated group (P: < 0.05) as shown by zymography. Our results suggest that depression of MMP-2 activity and increased LOX expression may be one of the causes of the cystogenesis of PCO.
Henmi
H
H
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo 060-0061, Japan.
Endo
T
T
Nagasawa
K
K
Hayashi
T
T
Chida
M
M
Akutagawa
N
N
Iwasaki
M
M
Kitajima
Y
Y
Kiya
T
T
Nishikawa
A
A
Manase
K
K
Kudo
R
R
D000735:Androstenedione / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004549:Elastin / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D010053:Ovary / Q000201:enzymology; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000201:enzymology*; D011374:Progesterone / Q000097:blood; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
D012333:RNA, Messenger; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D003094:Collagen; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; D020778:Matrix Metalloproteinase 2