Regulation of aromatase activity of stromal cells derived from human adipose tissue

Stromal cells derived from human sc adipose tissue and maintained in monolayer culture aromatize androstenedione to estrogens. Incubation of such stromal cells with dexamethasone (2.5 × 10⁻⁷ M) in medium that contained fetal calf serum (15%) resulted in a detectable increase in aromatase activity after 3 h and a 30-fold increase in enzyme activity by 18 h; this level was maintained through 48 h with a slight decline by 72 h. The effect of dexamethasone was diminished greatly when serum was removed from the culture medium. Incubation of stromal cells in medium without fetal calf serum for 24 h with (Bu)₂cAMP (1 mM) resulted in a 15-fold increase in aromatase activity; the effect of (Bu)₂cAMP was diminished by 70% when fetal calf serum (15%) was present in the culture medium. The time course of induction of aromatase activity of stromal cells maintained in medium without serum in response to (Bu)₂cAMP differed strikingly from that of aromatase induction of stromal cells incubated in serum-containing medium in response to dexamethasone. Aromatase activity of cells incubated with (Bu)₂cAMP continued to increase over an 8-day period, at which time enzyme activity was increased by 200-fold. When stromal cells were incubated with (Bu)₂cAMP and dexamethasone for up to 72 h in the absence or presence of serum, no synergistic effect was observed. Aromatase activity of stromal cells maintained in the presence or absence of serum was unaffected after incubation for 5 days with ovine FSH, human CG, bovine PRL, human GH, or soterenol. On the other hand, incubation of cells for 5 days with cholera toxin (10 μg × ml₋₁) or l-methyl-3-isobutylxanthine (0.1 mM) resulted in a marked increase in aromatase activity; the effect of these agents was diminished greatly when serum was present in the culture medium. The basal level of aromatase activity also was increased in stromal cells incubated for 5 days in serum-free medium. The findings that dexamethasone failed to increase stromal cell cAMP levels, that serum inhibited the stimulation of aromatase activity by (Bu)₂cAMP, and that the time courses of aromatase induction by (Bu)₂cAMP and dexamethasone were markedly different are suggestive that different molecular events mediate aromatase induction by glucocorticosteroids and cAMP.