TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS ENKEPHALINASE (EC-3.4.24.11) GENE-EXPRESSION IN HUMAN ENDOMETRIAL STROMAL CELLS AND SEX SKIN FIBROBLASTS IN CULTURE

This study was conducted to evaluate the negative regulation of enkephalinase by an endogenously produced peptide, namely transforming growth factor-beta1 (TGFbeta1). We found that TGFbeta1 acts in human endometrial stromal cells and sex skin fibroblasts in culture to cause a striking decrease (60% to >90% in 3-7 days) in the specific activity of enkephalinase (membrane metalloendopeptidase; EC 3.4.24.11) by reducing the levels of enkephalinase mRNA and protein. Platelet-derived growth factor caused a slight reduction in enkephalinase specific activity in endometrial stromal cells; epidermal growth factor caused a slight decrease in enkephalinase specific activity in sex skin fibroblasts. In studies in which TGFbeta1 treatment and [S-35]methionine labeling were conducted simultaneously, radiolabeling of enkephalinase was decreased. When proteins were radiolabeled with [S-35] methionine before treatment with TGFbeta1, the extent of enkephalinase radiolabeling was similar to that in nontreated cells. These findings are indicative that TGFbeta1 acts to decrease enkephalinase activity by a reduction in gene transcription or mRNA stability and not by accelerated degradation of enkephalinase protein.