Stimulation of lysyl oxidase (EC 1.4.3.13) activity by testosterone and characterization of androgen receptors in cultured calf aorta smooth-muscle cells.
Previous studies have indicated a greater incidence of atherosclerotic cardiovascular disease in men than in women of child-bearing age, suggesting that vascular interactions with sex steroids may effect pathogenesis in these cases. In the present study, it was found that the presence of 10-100 nM-testosterone in the growth medium of calf aortic smooth-muscle cells in culture stimulates lysyl oxidase activity approx. 2.5-fold in the medium and 5.5-fold in the fraction bound to the cell layer. Androgen receptors were identified in these cultured smooth-muscle cells, and their properties were very similar to those in the cytosolic fraction of whole bovine aortic tissue. These receptors appeared to be specific for androgen, of high affinity (Kd = 0.4 nM) and of low capacity (9000 sites/cell). The present results indicate that the aortic smooth-muscle cell is a cellular target for androgens, and thus raise the possibility that the development of fibrotic arterial lesions involving the deposition of excess collagen may in part be regulated by androgen-mediated stimulation of collagen cross-linkage formation as catalysed by lysyl oxidase.
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D004790:Enzyme Induction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis*; D011944:Receptors, Androgen / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*
D011944:Receptors, Androgen; D013739:Testosterone; D009277:Nandrolone; C100075:mibolerone; D000594:Amino Acid Oxidoreductases; D008249:Protein-Lysine 6-Oxidase