Effects of insulin on cultured rat brain cells: stimulation of ornithine decarboxylase activity

Growth-promoting peptide hormones, including growth hormone and insulin, stimulate rat brain ornithine decarboxylase (ODC; EC 4.1.1.17) activity in vivo (Roger et al., 1974; Roger and Fellows, 1980). To determine if this is a result of a direct action on brain, we have investigated the effect of peptide hormones in primary cell cultures of brain from fetal rats of 20 days gestational age. Significant stimulation of ODC activity was observed 4 h after administration of porcine insulin and bovine growth hormone. On a molar basis, growth hormone was less potent than insulin. By contrast, glucagon, enkephalin, and angiotensin II did not stimulate ODC in this system. At 25 ng/ml, insulin stimulated ODC activity approximately threefold, with maximum stimulation of five- to sevenfold reached at 1 microgram/ml. After a 1-h lag, insulin-stimulated ODC activity increased to a maximum between 5 h and 8 h and returned to basal levels by 24 h. The apparent Km of ODC, 5.66 +/- 1.16 microM, was not significantly altered by insulin treatment, nor was any enzyme activator found in mediating insulin actions. Additional evidence suggests that insulin stimulation of ODC activity involves both de novo synthesis of the enzyme and a prolongation of ODC half-life by 50%. These findings, implicating insulin as a regulator of ODC activity in brain cells, suggest the possible involvement of insulin or an insulin-like peptide in the control of growth and development of the CNS.