Norepinephrine potentiates the mitogenic effect of growth factors in quiescent brown preadipocytes: Relationship with uncoupling protein messenger ribonucleic acid expression

Rat brown preadipocytes cultured in low serum conditions increase DNA synthesis and proliferate in response to serum and a variety of growth factors and hormones. Epidermal growth factor, platelet-derived growth factor, and acidic and basic fibroblast growth factors stimulate DNA synthesis in a dose-dependent manner and induce at least a 5-fold increase in [H-3]thymidine incorporation after 40 h of exposure. The physiological activator of brown adipose tissue, norepinephrine, has a low mitogenic effect per se, but increases DNA synthesis stimulation exerted by serum, epidermal growth factor, basic fibroblast growth factor, and the neuropeptide vasopressin. The addition of vasopressin plus norepinephrine greatly potentiates the mitogenic effect of growth factors to levels comparable to the effect of 10% serum. Preadipocytes cultured in the presence of these mitogen combinations (growth factor, vasopressin, and norepinephrine) express a differentiation marker, the uncoupling protein. Thus, our results show 1) that a variety of growth factors and hormones induce DNA synthesis in a synergistic fashion in brown preadipocytes in primary culture; and 2) there is evidence for a role of norepinephrine in the regulation of brown adipocyte proliferation, potentiating the action of serum and mitogens, besides its role in uncoupling protein messenger RNA expression.