FATTY-ACIDS INHIBIT ADRENOCORTICOTROPIN-INDUCED ADRENAL STEROIDOGENESIS

Unsaturated long chain far, acids modulate hormone secretion from a va riety of endocrine glands, including the adrenal cortex. Oleic acid an d linoleic acid have been shown to stimulate production of glucocortic oids in the absence of adrenocorticotropic hormone, but at a high conc entration appeared to inhibit the action of this hormone. In the prese nt study, the concentration dependence of the inhibitory actions of th ese two fatty acids was tested in collagenase-dispersed rat adrenal fa sciculata cells, and the effects of both lipids on cAMP production wer e also determined. Adrenocorticotropic hormone stimulated steroid prod uction from isolated cells approximately ten-fold above unstimulated c ells. Oleic and linoleic acid significantly inhibited the response to this hormone by 44% and 54%, respectively. The half-maximally effectiv e inhibitory concentration of both lipids was between 75-100 mu M. A m aximal concentration of adrenocorticotropic hormone increased cAMP sec retion 138-fold above unstimulated cells. Oleic and linoleic acids inh ibited the increase in cAMP secretion by 47% and 33%, respectively. It is concluded that pathophysiological concentrations of unsaturated fa tty acids inhibit the action of adrenocorticotropic hormone on the adr enal gland, and that the mechanism of action of the lipids may be part ly via inhibition of cAMP production.