Bovine adrenocortical cytochrome P-450(17 alpha). Regulation of gene expression by ACTH and elucidation of primary sequence.

摘要: In the steroidogenic pathway of adrenal cortex, 17 alpha-hydroxylase cytochrome P-450 (P-450(17 alpha)) is a major regulatory enzyme. Previous studies have shown that stimulation activity occurs upon treatment bovine adrenocortical cells in culture with adrenocorticotropic hormone (ACTH), via cAMP, due to an increase enzyme concentration. Alterations levels this result pronounced changes pattern steroids produced, potent glucocorticoid cortisol, as well sex steroids, being products alpha-hydroxylated steroid precursors. present study, identification and sequencing two cloned DNA molecules, pB17 alpha-1 pcD17 alpha-2, which are complementary mRNA sequences encoding cortex P-450(17 alpha), reported. Clone alpha-2 contains open reading frame coding for complete amino acid sequence alpha) consists 509 acids has molecular weight 57,251. By comparison other forms P-450, we conclude member previously unidentified family within multigene superfamily. Single human species approximately equal 1850 bases length hybridize these clones. Regulation concentration RNA been studied using culture. Treatment ACTH or dibutyryl cAMP causes content little 2 h, its increases greater than 20-fold by 8 h. contrast, enzymes respond more slowly ACTH. Actinomycin D cycloheximide block induction RNA, indicating regulation controlled at level transcription requires ongoing protein synthesis.