Time-Dependent Biphasic Response of Aromatase to Dexamethasone in Cultured Human Skin Fibroblasts*

Publisher Website
Google Scholar
Abstract
Human genital skin fibroblasts grown in cell culture possess aromatase activity and,therefore, provide a model to investigate the molecular mechanisms that control aromatase in extraglandular tissues. Following the observation by other investigators that glucocorticoids stimulated aromatase activity in cultured stromal-vascular cells from adipose tissue, we examined the influence of dexamethasone (DEX) on aromatase in cultured skin fibroblasts. Preincubation of skin fibroblasts with DEX stimulated aromatase expression in all cell strains. In time-course studies, aromatase activity showed a biphasic curve, with peak levels at 12 h and a return to baseline levels by 72 h. When DEX was removed after 12 h, aromatase activity could be completely restimulatedby DEX only after a period of 60–72 h. The DEX stimulation appeared to involve glucocorticoid receptor function, since the concentration of DEX required for half-maximal stimulation of aromataseactivity (4.2 nM) was similar to the dissociation constant (Kd, 4.3 nM) of the receptor (for DEX). Actinomycin D and cycloheximide (CHX) inhibited DEX stimulation of aromatase when they were present in the preincubation and assay media. When cells were preincubated with DEX andCHX and then washed free of CHX and DEX before the assay, superinduction of aromatase activity occurred. Our data concerning the time course and superinduction of aromatase activity by DEX are in contrast to the findings reported by others for adipose tissue stromal-vascular cells and suggestthat the mechanisms for the control of aromatase in extraglandular tissue may vary significantly in different tissues.