Stimulation of steroidogenesis in cultured rat adrenocortical cells by
unsaturated fatty acids.
Sarel, Ina, and Eric P. Widmaier.
DEPARTMENT OF BIOLOGY, 5 CUMMINGTON ST., BOSTON UNIVERSITY BOSTON, MA
02215
APStracts 2:0019R, 1995.
The hypothesis was evaluated that the stimulatory action of free fatty acids
(FFA) in the hypothalamic/pituitary/adrenocortical (HPA) axis occurs in part
at the adrenal cortex. Pathophysiological concentrations of oleic and
linoleic, but not stearic or caprylic acids, stimulated steroidogenesis from
cultured rat adrenocortical cells (EC50, 60 and 120 mM, respectively) with a
latency of 90 minutes. Maximal stimulation of steroidogenesis by both acids
was <50% that produced by ACTH, and was blocked by cycloheximide. The maximal
steroidogenic response to ACTH was inhibited 50% by oleic acid. The actions
of oleic and linoleic acids were not associated with an increase in cAMP
secretion, but appeared to require intracellular oxidation. None of the
lipids influenced cell viability or the corticosterone RIA. The latency of
the steroidogenic response, the putative requirement for intracellular
oxidation, and the apparent lack of involvement of cAMP suggest a mechanism
of action of FFA distinct from that of ACTH, yet still requiring protein
synthesis. It is concluded that the modulation of steroidogenesis by these
abundant naturally-occurring lipids may be an important component of the
control mechanisms within the HPA pathway in disorders of lipid homeostasis
(e.g., obesity, starvation, or diabetes).
Received 26 September 1994; accepted in final form 18 January 1995.
APS Manuscript Number R558-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative Comp.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.