The effect of free fatty acids [FFAs (saturated (S) and unsaturated (U))] on dexamethasone binding in vitro using liver cytosol from rainbow trout was examined. 2. All UFFAs but none of the SFFAs tested suppressed binding. This suppression is dose-dependent and correlated roughly with the degree of unsaturation of the FFAs. 3. Scatchard analysis indicated that the addition of linoleic C18:2 (150 microM) increased the dissociation constant (Kd = 5.1 +/- 0.4 x 10(-8) M vs control of 1.7 +/- 0.3 x 10(-8) M) but minimally affected the binding capacity (Bmax = 68 +/- 6.2 vs control of 88 +/- 15.2 fmol/mg protein) suggesting C18:2 caused a conformational change of the receptor. 4. Lineweaver-Burk plot revealed a mixed non-competitive type of inhibition by C18:2. 5. Free acid appeared to be required for inhibition as esterification or derivatization of the acid greatly diminished its potency. 6.C18:2 also promotes the dissociation of bound [3H]-dexamethasone from the steroid-receptor complex but slower in rate and lesser in magnitude compared to that caused by dexamethasone or the glucocorticoid antagonist RU 38486. 7. UFFAs and some of their derivatives can thus modulate glucocorticoid receptor function in vitro and might play essential roles in regulating glucocorticoid action in fish as well. 8. These fatty acids presumably acts at a site different from that of the glucocorticoid binding site.
