Effect of human growth hormone and insulin on [3H]thymidine incorporation, cell cycle progression, and cyclin D expression in 3T3-F442A preadipose cells.
Cellular growth- and cyclin D expression-regulating activities of GH and insulin were investigated in 3T3-F442A preadipose cells under serum-free culture conditions. The present report provides evidence that the proliferative potential of 3T3-F442A cells is reduced by GH in a time- and concentration-dependent manner based on [3H]thymidine incorporation assay and cell cycle analysis. In contrast, treatment of 3T3-F442A cells with insulin resulted in cellular proliferation. The insulin-induced proliferation of 3T3-F442A cells was diminished in the presence of GH. In an effort to define biochemical events relevant to the regulatory activities of GH and insulin on the proliferation of 3T3-F442A cells, the effects of these peptides on the expression of cyclin D were studied using Western blotting. Treatment of 3T3-F442A cells with insulin led to an increase in cyclin D expression relative to that in untreated cells. The insulin-elicited expression of cyclin D was time and dose dependent. In addition, the ability of insulin to induce cyclin D expression was reduced by GH. Our experimental results indicate that proliferation of 3T3-F442A cells was regulated by GH and insulin. The regulatory effects of GH and insulin are mediated at least in part by the alternating expression of cyclin D protein.
Tang
B
B
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Jeoung
D I
DI
Sonenberg
M
M
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D019938:Cyclin D1; D016213:Cyclins / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D015513:Oncogene Proteins / Q000096:biosynthesis*; D016196:S Phase / Q000187:drug effects
D016213:Cyclins; D007328:Insulin; D015513:Oncogene Proteins; D019938:Cyclin D1; D013006:Growth Hormone; D004247:DNA