Effect of thyroid phospholipids on the interaction of thyrotropin with thyroid membranes

Various lipids extracted from bovine thyroid glands were tested for their ability to affect the binding of 125I-labeled thyrotropin to bovine thyroid membranes. The most potent inhibitors were the acidic phospholipids in the order cardiolipin greater than phosphatidylglycerol greater than phosphatidylinositol greater than phosphatidylserine. Other phospholipids, neutral lipids, and neutral glycolipids were ineffective. As reported previously [mullin, B. R., Pacuszka, T., Lee, G., Kohn, L. D., Brady, R. O. & Fishman, P. H. (1978) Science 199, 77--79], thyroid gangliosides also inhibited thyrotropin binding but not as effectively as phospholipids. In addition, the mode of action of these two classes of acidic lipids was different. When thyroid membranes were preincubated with the phospholipids and then separated by centrifugation, their ability to bind thyrotropin was still diminished. In contrast, gangliosides appear to interact with the hormone and not with the membranes. The effect of phospholipids on thyroid membranes was further examined by incubating the membranes with phospholipase A. The treated membranes now bound more labeled hormone. These results suggest that certain acidic phospholipids, which are present in only small amounts in thyroid membranes, influence the state of the thyrotropin receptor and its ability to bind thyrotropin.