Protein synthesis requirement for acute ACTH stimulation of adrenal corticosteroidogenesis.
The rapid, cAMP mediated increase produced by ACTH in adrenal corticosteroidogenesis depends also on the rapid synthesis of protein. This obligatory involvement of protein synthesis has been established in several laboratories mainly on the basis of studies demonstrating a parallelism, under a variety of experimental conditions, of the capacity of adrenal cells to synthesize protein with their ability to increase steroid production in response to ACTH or cAMP. More recent correlative studies have disclosed the existence of two proteins, denoted as p and i. Protein i appears only in ACTH or cAMP stimulated cells and with the same time course and ACTH dose response as the increase in corticosteroid synthesis. Protein p, which closely resembles i in molecular weight and primary structure but differs in pI, is synthesized only in unstimulated cells. Neither the function of these two proteins nor the exact nature of the interplay of their synthesis on regulation has been established, although it seems reasonably certain that i is stimulatory rather than p inhibitory. The protein glycosylation inhibitor tunicamycin was found to inhibit the ACTH produced increase in steroidogenesis and also to inhibit the synthesis of protein i under conditions which did not inhibit overall protein synthesis. Therefore it seems probable that i is an N-glycosylated form of protein p and that adrenal cells are unresponsive to acute ACTH action if they are incapable of synthesizing glycosylated proteins specifically.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis; D066298:In Vitro Techniques; D014176:Protein Biosynthesis; D051381:Rats; D014415:Tunicamycin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D006023:Glycoproteins; D014415:Tunicamycin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP