Hormonal regulation of the S14 gene in 3T3-F442A cells.

Abstract

3T3-F442A cells differentiate from preadipocytes to adipocytes when cultured in medium containing fetal calf serum and insulin. We examined the regulation of the S14 gene in 3T3-F442A preadipocytes and adipocytes to determine whether these cells would be a good in vitro model to define the regulation and function of the S14 protein (17,000 Mr; 4.9 pI). Expression of mRNAs14 (1.12 kilobases) in mouse liver is regulated by both thyroid hormone (T3) and glucocorticoids. Accordingly, we examined the T3 and glucocorticoid regulation of S14 gene expression in 3T3-F442A cells. Neither T3 or the glucocorticoid agonist, dexamethasone (DEX) induced mRNAs14 in 3T3-F442A fibroblasts. While DEX induced mRNAs14 greater than 60-fold in 3T3-F442A adipocytes after a 72-h treatment, T3 was found to have no effect on S14 gene expression in adipocytes. These results indicate: 1) that S14 gene expression is dependent on the differentiation state of 3T3-F442A cells; and 2) that of the two hormones regulating mRNAs14 expression in vivo, only the glucocorticoid regulatory mechanism is operative in 3T3-F442A adipocytes. Characterization of the glucocorticoid-mediated regulation of S14 gene expression showed that DEX induced mRNAs14 significantly within 30 min, but required 72 h of hormone treatment to reach maximal levels of expression. The glucocorticoid-mediated increase in mRNAs14 was due to activation of S14 gene transcription. While glucocorticoid analogs induced mRNAs14, mineralocorticoids and sex steroids failed to induce mRNAs14 in adipocytes. These studies suggest that glucocorticoids act directly on the S14 gene through the glucocorticoid receptor to regulate S14 gene expression in 3T3-F442A.(ABSTRACT TRUNCATED AT 250 WORDS)