title: Hormonal regulation of matrix metalloproteinase 9/gelatinase B gene expression in rabbit uterine cervical fibroblasts.
abstract: Since the degradation of uterine cervical extracellular matrix is an essential process in cervical ripening and dilatation at term, we examined the effect of pregnancy on the level of pro-matrix metalloproteinase 9 (proMMP-9)/progelatinase B in the rabbit uterine cervix and its regulation in uterine cervical fibroblasts. Uterine cervices shortly before term parturition contained high levels of proMMP-9 compared with those of nonpregnant rabbits. Uterine cervical fibroblasts prepared from rabbits at 23 days of gestation did not produce proMMP-9; in contrast, interleukin (IL)-1 alpha, IL-1 beta, or phorbol 12-myristate 13-acetate (PMA) induced proMMP-9 production along with an increase of proMMP-9 mRNA, and the IL-1-mediated induction of proMMP-9 was synergistically enhanced by PMA. On the other hand, physiological concentrations of progesterone suppressed IL-1-and/or PMA-mediated production of proMMP-9 in a dose-dependent manner. This suppressive effect of progesterone on proMMP-9 production was accompanied by a decrease in matrix metalloproteinase 9 (MMP-9) mRNA, indicating that progesterone down-regulates the production of proMMP-9 at the transcriptional level. These results indicate that in the rabbit uterine cervix, IL-1 alpha and IL-1 beta are effective inducers of the proMMP-9 production, and progesterone is a physiological suppressor. Thus, MMP-9 and progesterone are very likely to play essential roles in cervical ripening and dilatation in the rabbit, and the production of MMP-9 in the cervix is finely regulated during pregnancy.
authors.affiliation: Department of Biochemistry, Tokyo University of Pharmacy and Life Science, School of Pharmacy, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imada
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Namiki
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000201:enzymology*; D003001:Cloning, Molecular; D017364:Collagenases / Q000235:genetics*; D005260:Female; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011817:Rabbits
chemical_list: D006728:Hormones; D007375:Interleukin-1; D012333:RNA, Messenger; D011374:Progesterone; D017364:Collagenases; D020780:Matrix Metalloproteinase 9