Possible Interaction: Aminoglutethimide and Adrenocorticotropic Hormone

“It indicates that aminoglutethimide directly inhibits ACTH secretion.”

“This last effect of ACTH was concentration‐dependently abolished by both aminoglutethimide and cyanoketone, which blocks early steps of steroid synthesis, but not by metyrapone, an inhibitor of 11β‐hydroxylase.”

“Stimulation of the protein kinase A pathway by simultaneous incubation of ACTH (10 nM) or forskolin (10 microM) together with AG was not able to overcome the steroid biosynthesis blockade, but reversed the inhibitory effects of AG on the ACTH-R mRNA expression.”

“ Aminoglutethimide given during treatment with ACTH decreased urinary aldosterone and blood pressure and increased PRA, with minimal effects on plasma cortisol or urinary 17-hydroxycorticosteroids.”

“Several of the differentially expressed transcripts, such as AGT , are associated with processes modulating steroidogenic response of adrenocortical cells to ACTH.”

“Addition of aminoglutethimide together with ACTH resulted in a smaller increase than that achieved with ACTH alone.”

“ ACTH administration to rats treated with DEX + aminoglutethimide resulted in decreased adrenal apoE mRNA despite greatly increased adrenal cholesterol content.”

“The increase in the levels of LDL … and HMG-CoA reductase mRNAs produced by ACTH was reduced by …-administration of aminoglutethimide while, at the same time, the adrenal cholesterol content of rats treated with both … and ACTH was significantly increased compared with that in groups treated with ACTH alone.”

“ Aminoglutethimide at concentrations from 0.1 to 5 nM is able to inhibit the cortisol release elicited by adrenocorticotropic hormone (ACTH) (from 2.5 to 50 ng/ml) in guinea-pig adrenal cortex slices.”

“Coadministration of aminoglutethimide with ACTH also resulted in a decrease (65%) in reductase activity compared to that in NaCl-treated animals.”

“However, coadministration of aminoglutethimide , in contrast to cycloheximide, with ACTH not only prevented the reductase mRNA level increase produced by ACTH, but also resulted in a 30% decrease in the reductase mRNA level compared to that in controls injected with 0.15 M NaCl.”

“Thus, we have shown that both cycloheximide and aminoglutethimide can prevent the enhancing effect of ACTH on HMG-CoA reductase activity, but their modes of action differ.”