An antiprogesterone, onapristone, enhances the gene expression of promatrix metalloproteinase 3/prostromelysin-1 in the uterine cervix of pregnant rabbit.
Using a progesterone receptor antagonist, onapristone/ZK 98.299, we examined the in-vivo effects of progesterone on the function of uterine cervix during pregnancy. Onapristone was intravenously administered to pregnant rabbits on day 20 post coitum. After 24 h, the antiprogesterone increased the wet weight of the uterine cervix and decreased the DNA concentration in the cervix. In-situ hybridization also indicated that antiprogesterone augmented the expression of matrix metalloproteinase (MMP)-3/stromelysin-1 mRNA in the uterine cervix. These changes are very similar to those observed and reported thus far in ripened and dilated uterine cervix. These results suggest that during pregnancy, progesterone closely participates in the maintenance of the function of uterine cervix by preventing the production of MMPs and thereby destruction of extracellular matrix, and thus add support to the theory that antiprogesterone has the potential to accelerate for the uterine cervical ripening and dilatation.
Imada
Keisuke
K
Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Sato
Takashi
T
Hashizume
Kazuyoshi
K
Tanimoto
Akihide
A
Sasaguri
Yasuyuki
Y
Ito
Akira
A
D000818:Animals; D002584:Cervix Uteri / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006067:Gonanes / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000096:biosynthesis*; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits
D006067:Gonanes; D006727:Hormone Antagonists; D011374:Progesterone; D019278:Matrix Metalloproteinase 3; C053238:onapristone