Quantitative comparison of aromatase induction by dexamethasone in fibroblasts from a patient with familial cortisol resistance and a patient with cortisol hyperreactive syndrome.
The ability of dexamethasone to induce aromatase activity was tested in fibroblasts from a patient with familial cortisol resistance, a patient with cortisol hyperreactive syndrome, and five normal subjects. Dexamethasone increased enzyme activity in all cases in a concentration-dependent manner (over a range of 1-1000 nmol/L). In fibroblasts from a patient with familial cortisol resistance, the response curve of dexamethasone-induced aromatase activity was shifted to the right compared to that of normal cells. However, the maximal induction of the enzyme at 1 mumol/L dexamethasone was unchanged in cortisol-resistant fibroblasts. On the other hand, in fibroblasts from the patient with the cortisol hyperreactive syndrome, the half-maximal effect of dexamethasone was similar to that in normal cells, but maximum induction of aromatase activity was 2 times greater than that in normal cells. The glucocorticoid antagonist RU 486 inhibited dexamethasone-induced aromatase activity in these patients' cells and in normal cells in a concentration-dependent manner, indicating that the altered effects of dexamethasone on aromatase induction observed in each cell type were mediated through glucocorticoid receptors.
Iida
S
S
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Moriwaki
K
K
Fujii
H
H
Gomi
M
M
Tsugawa
M
M
Nakamura
Y
Y
Kitani
T
T
Tarui
S
S
D001141:Aromatase / Q000096:biosynthesis*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance; D004700:Endocrine System Diseases / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology*; D007700:Kinetics; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D013577:Syndrome
D015735:Mifepristone; D003907:Dexamethasone; D001141:Aromatase; D006854:Hydrocortisone