STIMULATION OF STEROIDOGENESIS IN CULTURED RAT ADRENOCORTICAL-CELLS BY UNSATURATED FATTY-ACIDS

The hypothesis that the stimulatory action of free fatty acids (FFA) i n the hypothalamic-pituitary-adreno cortical (HPA) axis occurs in part at the adrenal cortex was evaluated. Pathophysiological concentration s of oleic and linoleic acids, but not stearic or caprylic acid, stimu lated steroidogenesis from cultured rat adrenocortical cells (concentr ations eliciting 50% of maximal response, similar to 60 and 120 mu M, respectively), with a latency of 90 min. Maximal stimulation of steroi dogenesis by both acids was <50% of that produced by adrenocorticotrop ic hormone (ACTH) and was blocked by cyclohedmide. The maximal steroid ogenic response to ACTH was inhibited similar to 50% by oleic acid. Th e actions of oleic and linoleic acids were not associated with an incr ease in adenosine 3',5'-cyclic monophosphate (cAMP) secretion but appe ared to require intracellular oxidation. None of the lipids influenced cell viability or corticosterone radioimmunoassay. The latency of the steroidogenic response, the putative requirement for intracellular ox idation, and the apparent; lack of involvement of cAMP suggest a mecha nism of action of FFA distinct from that of ACTH, yet still requiring protein synthesis. It is concluded that the modulation of steroidogene sis by these abundant naturally occurring lipids may be an important c omponent of the control mechanisms within the HPA pathway in disorders of lipid homeostasis (e.g., obesity, starvation, or diabetes).