Estrogen formation in stromal cells of adipose tissue of women: induction by glucocorticosteroids.
Stromal cells prepared from adipose tissue of women were maintained in monolayer culture to study the regulation of aromatase activity by hormones. Aromatase activity was stimulated 20- to 100-fold by dexamethasone at a concentration of 250 nM. Half-maximal stimulation of aromatase activity was attained at a dexamethasone concentration of 2.7 nM. The stimulatory effect of dexamethasone was apparent after a preincubation time of 4 hr, and stimulation was maximal after 24 hr of preincubation. The stimulatory effect of dexamethasone was observed only when fetal calf serum also was present in the culture medium. Of the various steroids tested, dexamethasone was the most potent in stimulating aromatase activity. Cortisol was less effective than dexamethasone, whereas corticosterone, at a concentration of 250 nM, caused only a small stimulation of aromatase activity. Progesterone and deoxycorticosterone (250 nM) did not affect aromatase activity. Cytosolic fractions prepared from stromal cells that had been maintained in monolayer culture were found to contain a homogenous population of sites that specifically bound [3H]dexamethasone with relatively high affinity (Kd = 2.9 nM) and low capacity (38 fmol per mg of protein). The stimulatory effect of dexamethasone on aromatase activity was prevented by simultaneous incubation with cortisol 21-mesylate (0.1-10 microM), a compound known to block the binding of glucocorticosteroids to cytoplasmic receptors. The stimulatory effect of dexamethasone also was prevented by incubation of the cells with cycloheximide or actinomycin D. These findings are suggestive that glucocorticosteroids act to increase aromatase activity in stromal cells by inducing the synthesis of new enzyme protein.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D001141:Aromatase / Q000096:biosynthesis*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D010088:Oxidoreductases / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003609:Dactinomycin; C027504:cortisol 21-mesylate; D003907:Dexamethasone; D003513:Cycloheximide; D010088:Oxidoreductases; D001141:Aromatase; D006854:Hydrocortisone