Modulation of glucocorticoid binding to rat liver cytosol receptor by lipid-soluble extracts from the serum of AIDS patients.
The total liposoluble extract of sera from AIDS patients, IVC1 and IVD stages, containing cortisol and free fatty acids (FFA) inhibited [3H]dexamethasone binding to a lesser extent than did the same quantity of total liposoluble extract of sera from healthy men. FFA isolated from extracts of AIDS sera by Sephadex LH20 chromatography had less effect on [3H]dexamethasone binding to rat liver glucocorticoid receptor than those extracted from sera of healthy men. These results suggest the presence in sera of AIDS patients of a liposoluble substance which could be limiting the inhibitory effect of FFA on [3H]dexamethasone binding to glucocorticoid receptor by inducing a conformational change in glucocorticoid receptor that could alter the biological action of glucocorticoids. The pathological consequence could be the apparent contradiction of high cortisolemia and clinical symptoms of adrenal insufficiency that have been observed in AIDS patients.
Vallette
G
G
INSERM U224 CNRS, Faculté de Médecine Xavier Bichat, Paris, France.
Sumida
C
C
Thobie
N
N
Nunez
E A
EA
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D000328:Adult; D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012995:Solubility
D005230:Fatty Acids, Nonesterified; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone