| Abstract: | Studies were carried out to define the mechanism of action of growth hormone on adrenocortical steroidogenesis in hypophysectomized female rats. ACTH administration for 7 days increased corticosterone secretion in vivo and corticosterone production by adrenal tissue in vitro. Adrenal mitochondrial and microsomal cytochrome P-450 concentrations as well as the activities of cytochrome P-450-dependent enzymes (cholesterol sidechain cleavage, 11beta-hydroxylase, 21-hydroxylase) were also increased by ACTH. Administration of bovine growth hormone alone to hypophysectomized rats had no effect on any of the parameters evaluated. However, when given in combination with ACTH, growth hormone synergistically enhanced the effects of ACTH on cholesterol sidechain cleavage activity and corticosterone secretion. The magnitude of the pregnenolone-induced difference spectrum in adrenal mitochondria, indicative of cholesterol binding to cytochrome P-450, was also increased by growth hormone, but neither cytochrome P-450 content nor the activities of other steroidogenic enzymes were affected. The results indicate that growth hormone interacts with ACTH to promote corticosterone secretion by increasing the association of cholesterol with adrenal mitochondrial cytochrome P-450, thereby increasing the activity of cholesterol sidechain cleavage, the rate-limiting step in steroidogenesis. |
