Keloids are dermal tumors which occur in response to trauma. An hereditary predisposition to keloid formation occurs with high frequency in black populations. In vivo, prolonged proliferation of fibroblasts and over-production of collagen and proteoglycans are observed. We are attempting to identify the primary gene defect causing this tumor and its mode of action by studying growth and matrix metabolism of cultured fibroblasts derived from keloids and from normal skin and scar tissue. We have shown that cultured fibroblasts derived from keloid tissue differ from human fibroblasts derived from normal scar tissue and dermis in their response to hydrocortisone: the growth of normal fibroblasts is stimulated whereas keloid cells are inhibited, collagen and proteoglycan production are much less inhibited in keloid than in normal cells and system A amino acid transport is stimulated two-fold in normal cells but 10-fold in keloid-derived fibroblasts. Regulation of all of these processes is mediated by the glucocorticoid receptor in both normal and keloid cells, but the altered response to hydrocortisone by keloid cells is not due to differences in number of glucocorticoid receptors or the steroid binding constant. We are continuing the examination of the mechanism of glucocorticoid action in these cell types by studying activation of the steroid-receptor complex, translocation of the complex to the nucleus and binding of the complex to chromatin. We are investigating the interdependency of the various phenotypes differentially affected by hydrocortisone in keloid cells. Preliminary studies in which amino acid uptake via system A was blocked with methyl aminoisobutyric acid suggest that glucocorticoid-induced changes in matrix metabolism and growth are not caused by increased amino acid uptake. We are examining the specific radioactivity of amino acid incorporated into newly synthesized protein and precursor pools as a first step in determining the metabolic fate of amino acid entering via system A.