GROWTH-HORMONE AND ADIPOSE DIFFERENTIATION - GROWTH HORMONE-INDUCED ANTIMITOGENIC STATE IN 3T3-F442A PREADIPOSE CELLS

An additional activity for pituitary growth hormone is described-i.e., the in vitro induction of an antimitogenic state in murine 3T3-F442A preadipocyte fibroblasts. We previously developed a serum-free, hormonally defined medium permissive for the adipose differentiation of 3T3-F442A cells. When 3T3-F442A fibroblasts were maintained in serum-free medium without insulin but with growth hormone (2 nM), typical adipose differentiation did not occur. However, we found that growth hormone induced a state of cellular refractoriness to the mitogenic stimulus of fetal bovine serum as assayed by de novo DNA synthesis. The mitogen refractory condition (i.e., the antimitogenic state) was time-dependent (half maximal at ≃2.5 days) and growth hormone concentration-dependent (half maximal and maximal at ≃0.05 and 2.0 nM, respectively). The antimitogenic state was specifically induced by growth hormone and was not mediated by insulin-like growth factor I or prolactin. The growth hormone-induced antimitogenic state was completely reversible. The antimitogenic state was not induced by growth hormone in 3T3-C2 cells, a sister clone of 3T3 cells that exhibits essentially no adipose conversion. The kinetics for growth hormone-dependent commitment to adipose differentiation and induction of the antimitogenic state were similar. We suggest a relationship of growth hormone-induced antimitogenic state and the growth hormone-induced adipose differentiation of 3T3-F442A cells.