Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase.

Publisher Website
Google Scholar
Abstract
In Y1 [mouse] adrenocortical tumor cells, ACTH, cyclic[c]AMP and 8-bromoadenosine 3'',5''-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxylyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half-maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 h after the addition of these agents, reached a maximum between 4 and 6 h, and then declined. Mutant clones were impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cAMP. Adenylate cyclase and cAMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In Y1(Kin) mutants with altered cAMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. cAMP-dependent protein kinase apparently also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cAMP-dependent protein kinase activity. The pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity apparently diverge subsequent to activation of the protein kinase.