Metabolic Regulation of Steroidogenesis in Isolated Adrenal Cells of Rat

Publisher Website
Google Scholar
Abstract
The data presented with the isolated adrenal cells, in the present study, show that adrenocorticotropin in the physiological concentration range stimulates the synthesis of guanosine 3′:5′‐monophosphate (cyclic GMP), protein kinase activity, and steroidogenesis in a concentration‐dependent manner without detectable rise in the levels of adenosine 3′:5′‐monophosphate (cyclic AMP). Millimolar concentrations of cyclic AMP and cyclic GMP, which stimulate corticosterone synthesis, also activate kinase activity and steroidogenesis in a sigmoid concentration‐response manner. The process of phosphorylation activated by corticotropin, cyclic AMP and cyclic GMP is not inhibited by eyeloheximide or actinomyin D. It is therefore proposed that the hormonal responses mediated by cyclic GMP and cyclic AMP are via the protein kinase enzymatic steps, and the inhibitory effect of' cycloheximide and actinomycin D in corticotropin‐stimulated steroidogenesis follows this step. In conjunction with our previous observations that the biosynthetic steps from (20S)‐20‐hydroxycholesterol to corticosterone are neither inhibited by cycloheximide nor affected by cyclic GMP, it is inferred that the rate‐limiting step of adrenal steroidogenesis is the transformation of cholesterol to (20S)‐20‐hydroxycholesterol and this very step is regulated by cyclic GMP and cyclic AMP.Of further significance are the findings that micromolar concentrations of cyclic AMP and cyclic GMP, which do not stimulate steroidogenesis, effectively stimulate protein kinase activity in a concentration‐dependent manner. It is therefore concluded that all cyclic‐nucleotide‐dependent protein kinase activities of the cell are not necessarily related to steroidogenesis.

This publication has 21 references indexed in Scilit: