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Reproductive Endocrinology Center, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, California 94143
Address all correspondence and requests for reprints to: Dr. Pentti K. Siiteri, Reproductive Endocrinology Center, University of California, San Francisco, California 94143.
The regulation of 11β-hydroxysteroid dehydrogenase (11βHSD) was studied in cultured human skin fibroblasts. 11-Oxo-reductase activity was 5- to 10-fold higher than 11β-dehydrogenase activity. Cells treated with 100 nM dexamethasone (Dex) showed a 3-fold increase in the maximum velocity of both activities without a change in the Km values. Dex induction of 11βHSD was half-maximal at 48 h and was blocked by glucocorticoid receptor antagonists. Nonglucocorticoid steroids were ineffective. Removal of serum from the culture medium increased maximum velocity values up to 6-fold. Treatment of cells grown in the absence of serum with 8-bromo-cAMP, phorbol esters, or insulin decreased both 11βHSD activities. The effects of Dex treatment and serum removal were additive and were blocked by cycloheximide and actinomycin-D. In all experiments both 11βHSD activities were modulated in parallel. Both cortisone (200 nM) and cortisol increased the aromatase activity of fibroblasts in the presence of serum. Prior induction of 11βHSD by serum removal increased the potency of cortisone from 10–15% to 50% that of cortisol.
We conclude that 1) in human fibroblasts 11βHSD appears to be a single protein that is under multifactorial regulation; 2) 11βHSD may increase or decrease cortisol availability to glucocorticoid receptors; and 3) plasma cortisone levels may be important in assessing glucocorticoid status.
* This work was supported by NIH Grant CA-27702 (to P.K.S.).
Received October 24, 1990.
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