Studies were performed to evaluate a possible modulatory role of lipids on the binding of T, to rat liver nuclear receptors in vitro. Unsaturated fatty acids were potent inhibitors of the binding of ['261] T, to isolated rat liver nuclei. Doses (in pmol/L) causing a 50% inhibition of nuclear T, binding were 10 for palmitoleic acid, 11 for linoleic acid, 22 for oleic acid, 24 for arachidonic acid, and 37 for linolenic acid. Other lipids had less or no inhibitory activity. Unsaturated fatty acids reduced the affinity constant (K,) of the binding of T, to nuclear receptors to 57.4% f 11 .O% that of controls (mean + SE 1.04 f 0.14 v 1.97 + 0.23 lo9 L/M, n = 5: P < .02) but did not affect the maximal binding capacity (MBCI (1.47 f 0.20 v 1.55 + 0.10 lo-" M/L; NS). Evaporated ether extracts of rat liver homogenate pretreated with phospholipase A, for five to 20 minutes (that liberates unsaturated fatty acids from phospholipidsl demonstrated a progressive inhibition of nuclear T, binding with time when compared with ether extracts of untreated rat liver homogenate (F = 16.1; P -c -01). Evaporated, fatty-acid-rich ether extracts of human sera caused a dose-dependent inhibition in the binding of ['261] T, to nuclear T, receptors. Nuclear T, binding in the presence of extracts of 22 sera (0.1 mL-Eq aliquots) of patients with nonthyroid& illness (NTI) was 58.9% ? 4.9% (mean ? SE; range 17% to 107%) that of normal sera (100% + 6.2%. n = 9; P =z .0005); it was more that 2 SD below the normal mean in 12 (55%) patients. Inhibition of nuclear T, binding by NTI sera was correlated with the presence of a thyroid hormone-binding inhibititor (THBI) in these sera (r = .89; P < .0005). Evaporated ether extracts of NTI sera reduced the K, values of the binding of T, to nuclear receptors to 47.5% + 10.8% that of normal sera (n = 4: P < .Ol 1, without an effect on MBC. These various data suggest that unsaturated fatty acids can modulate thyroid hormone binding to its nuclear receptor in vitro. Whether or not fatty acids exert a similar effect in vivo is presently unknown. m 198i by Grune & Stratton, Inc. U NSATURATED FATTY ACIDS are important mod-
Studies With Lipids
Various lipids were purchased from Sigma Chemical Co, St Louis. They were dissolved in ethanol, and concentrations for use in