TY - JOUR
T1 - Characterization of the glucocorticoid receptor in human skin
AU - Leiferman, K. M.
AU - Schroeter, A.
AU - Kirschner, M. K.
AU - Spelsberg, T. C.
PY - 1983
Y1 - 1983
N2 - Because of the profound importance glucocorticoids have in dermatologic therapy, we studied the glucocorticoid receptor in human skin. A cytosol fraction was prepared from frozen skin by homogenization and centrifugation. When reacted with [3H]dexamethasone, this cytosol contained saturable, low-capacity binding. The glucocorticoid binding was stabilized by a protease inhibitor, phenylmethylsulfonylfluoride, and by sodium molybdate and was destroyed by trypsin. Sedimentation analysis of the glucocorticoid binding protein showed an 8S to 4S transition in high salt, a property of many known steroid hormone receptors. The binding was steroid specific, supporting the conclusion that this binding protein was a glucocorticoid receptor. The receptor molecule had a frictional ratio of 1.60 and a M(r) of about 226,000 under low-salt conditions (0.05 M KCl) and a frictional ratio of 1.86 and a M(r) of about 100,000 under high-salt conditions (0.3 M KCl) consistent with a nonglobular, elongated molecule. Isoelectric focusing showed that the receptor had 2 molecular species with isoelectric points of approximately 5.8 and 7.5. Quantitation of receptor in human skin showed 4-7 times more receptors in the epidermis and papillary dermis than in the lower dermis and nearly equal numbers in epidermis and papillary dermis. The concentration of receptors varied in different anatomic areas, with male foreskin showing the highest concentration, followed by female face, breast, and abdominal skin. Interestingly, the concentration of glucocorticoid receptors also varied with age; the highest levels were present at the extremes of life and a significantly lower level at midlife.
AB - Because of the profound importance glucocorticoids have in dermatologic therapy, we studied the glucocorticoid receptor in human skin. A cytosol fraction was prepared from frozen skin by homogenization and centrifugation. When reacted with [3H]dexamethasone, this cytosol contained saturable, low-capacity binding. The glucocorticoid binding was stabilized by a protease inhibitor, phenylmethylsulfonylfluoride, and by sodium molybdate and was destroyed by trypsin. Sedimentation analysis of the glucocorticoid binding protein showed an 8S to 4S transition in high salt, a property of many known steroid hormone receptors. The binding was steroid specific, supporting the conclusion that this binding protein was a glucocorticoid receptor. The receptor molecule had a frictional ratio of 1.60 and a M(r) of about 226,000 under low-salt conditions (0.05 M KCl) and a frictional ratio of 1.86 and a M(r) of about 100,000 under high-salt conditions (0.3 M KCl) consistent with a nonglobular, elongated molecule. Isoelectric focusing showed that the receptor had 2 molecular species with isoelectric points of approximately 5.8 and 7.5. Quantitation of receptor in human skin showed 4-7 times more receptors in the epidermis and papillary dermis than in the lower dermis and nearly equal numbers in epidermis and papillary dermis. The concentration of receptors varied in different anatomic areas, with male foreskin showing the highest concentration, followed by female face, breast, and abdominal skin. Interestingly, the concentration of glucocorticoid receptors also varied with age; the highest levels were present at the extremes of life and a significantly lower level at midlife.
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U2 - 10.1111/1523-1747.ep12519950
DO - 10.1111/1523-1747.ep12519950
M3 - Article
C2 - 6619566
AN - SCOPUS:0020521342
SN - 0022-202X
VL - 81
SP - 355
EP - 360
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -