Dexamethasone signaling is required to establish the postmitotic state of adipocyte development.
The clonal expansion phase of 3T3-L1 adipose conversion is a distinct mitotic period during which the initiation of differentiation occurs concomitant with a discrete set of mitotic divisions. During clonal expansion, a cocktail of adipogenic hormones, including the glucocorticoid dexamethasone, induced 3T3-L1 cells to progress from postconfluent adipoblasts to postmitotic adipocytes. It is reported here that expression of the growth arrest-associated gene 2 (gas2) discriminated reversible, postconfluent growth arrest from irreversible, postmitotic growth arrest. In the absence of dexamethasone, 3T3-L1 cells underwent mitoses but failed to establish postmitotic growth arrest, as evidenced by the persistence of elevated GAS2 mRNA. Moreover, the dexamethasone-deprived 3T3-L1 cells appeared to revert to postconfluent growth arrest, as judged by (a) their ability to reenter logarithmic growth under permissive conditions, and (b) their ability to undergo adipose conversion when subsequently challenged with a complete cocktail of adipogenic hormones. The growth potentiating factor-encoding gene, gas6, was shown to be an immediate-early target of dexamethasone. These findings reveal the requirement for dexamethasone in establishing the postmitotic state that accompanies differentiation. In addition, the results suggest that dexamethasone signaling influences the mitotic divisions of clonal expansion by determining the nature of the growth arrest state assumed upon exit from the cell cycle.
Shugart
E C
EC
Department of Biology, University of Virginia, Charlottesville 22903, USA.
Umek
R M
RM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000032:analysis; D013997:Time Factors; D000099255:Growth Arrest-Specific Protein 6
D015056:1-Methyl-3-isobutylxanthine; D003513:Cycloheximide; D003907:Dexamethasone; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D010726:Phosphodiesterase Inhibitors; D011506:Proteins; D012313:RNA; D000099255:Growth Arrest-Specific Protein 6; C099165:Gas2 protein, mouse