Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants.
Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MMPs). Analysis of conditioned media by zymography revealed latent and active forms of collagenase (MMP-1, EC 3.4.24.7), 72-kDa gelatinase A (MMP-2, EC 3.4.24.24), and 92-kDa gelatinase B (MMP-9, EC 3.4.24.35). These proteinases were identified by their M(r), their inhibition by tissue inhibitor of metalloproteinases, and the activation of their zymogens by trypsin or aminophenylmercuric acetate. In the absence of sex hormone, explants released large amounts of enzyme activities, as measured by densitometry of zymograms or in soluble assays. Physiological concentrations of progesterone (10-200 nM) almost totally abolished the release of collagenase, of total gelatinase activity, and of the active form of gelatinase B and largely inhibited the release of the active form of gelatinase A. These effects, which were antagonized by mifepristone (RU 38486), suggest that progesterone restrains endometrial tissue breakdown by blocking the secretion and activation of MMPs.
Marbaix
E
E
Cell Biology Unit, International Institute of Cellular and Molecular Pathology, Bruxelles, Belgium.
Donnez
J
J
Courtoy
P J
PJ
Eeckhout
Y
Y
D017364:Collagenases / Q000378:metabolism*; D004717:Endometrium / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D011374:Progesterone / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D009363:Neoplasm Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D011374:Progesterone; D017364:Collagenases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9