title: 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.
abstract: This study was conducted to evaluate the negative regulation of enkephalinase by an endogenously produced peptide, namely transforming growth factor-beta 1 (TGF beta 1). We found that TGF beta 1 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 TGF beta 1 treatment and [35S]methionine labeling were conducted simultaneously, radiolabeling of enkephalinase was decreased. When proteins were radiolabeled with [35S] methionine before treatment with TGF beta 1, the extent of enkephalinase radiolabeling was similar to that in nontreated cells. These findings are indicative that TGF beta 1 acts to decrease enkephalinase activity by a reduction in gene transcription or mRNA stability and not by accelerated degradation of enkephalinase protein.
authors.affiliation: Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235.
authors.forename: M L
authors.initials: ML
authors.lastname: Casey
authors.forename: J W
authors.initials: JW
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: P C
authors.initials: PC
authors.lastname: MacDonald
mesh_terms: D015152:Blotting, Northern; D002478:Cells, Cultured; D004717:Endometrium / Q000201:enzymology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D015260:Neprilysin / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010413:Penis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D015260:Neprilysin