I. Sarel et Ep. Widmaier, STIMULATION OF STEROIDOGENESIS IN CULTURED RAT ADRENOCORTICAL-CELLS BY UNSATURATED FATTY-ACIDS, American journal of physiology. Regulatory, integrative and comparative physiology, 37(6), 1995, pp. 1484-1490
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).