The antiglucocorticoid RU38486 is a potent accelerator of adipose conversion of 3T3-F442A cells.
We examined the effects of RU38486, a potent glucocorticoid and progestin antagonist, upon several aspects of 3T3-F442A adipocyte differentiation. RU38486 accelerated the onset of differentiation, as monitored by cell morphological changes, accumulation of lipid droplets and widespread increases in the rate of expression of several enzyme adipose markers and specific mRNAs. RU38486, at a maximal concentration of 1 microM, dramatically hastened the emergence of both fatty-acid synthetase (FAS) and glycerol-3-phosphate dehydrogenase (G3PDH) enzyme activities (550% and 450% above control values 4 days after confluence, respectively). RU38486 induction of G3PDH-specific activity ran parallel to an increase in G3PDH mRNA content (2.4-fold the control content 4 days after confluence). Moreover, RU38486-treated cells exhibited enhancement of adenylate cyclase sensitivity to both isoproterenol and ACTH (160% and 350% above control activities 8 days after confluence, respectively). While the level of expression of lipogenic markers reached similar values at the mature stage, RU38486 enabled cells to acquire hypersensitivity in terms of ACTH-stimulated adenylate cyclase activity. Similarly, adipsin gene expression was highly potentiated by the drug at day 15 post-confluence (5-fold the control value). RU38486 responsiveness observed in differentiating 3T3-F442A cells is dependent upon their prior developmental activation; none of the studied markers could be induced by the drug in the undifferentiating 3T3-C2 cell subclone. Finally, this antiglucocorticoid appears to be a useful tool for studies on adipose conversion in vitro; it could permit a re-evaluation of the role of glucocorticoids in the understanding of adipocyte development.
Fève
B
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INSERM U282, Hôpital Henri Mondor, Creteil, France.
Antras
J
J
Lasnier
F
F
Hilliou
F
F
Pairault
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D011416:Complement Factor D; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000502:physiology; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis; D050356:Lipid Metabolism; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000096:biosynthesis
D005938:Glucocorticoids; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone; D005993:Glycerolphosphate Dehydrogenase; D064429:Fatty Acid Synthases; D012697:Serine Endopeptidases; D011416:Complement Factor D; C493491:complement factor D, mouse; D000262:Adenylyl Cyclases