Interactions of Bovine Thyrotropin and Preparations of Human Chorionic Gonadotropin with Bovine Thyroid Membranes

Abstract

In view of the recent reports suggesting that human chorionic gonadotropin (hCG) may have intrinsic thyrotropic activity, the interaction of partially purified (hCG-c) and highly purified hCG (hCG-p) with bovine thyroid membranes was studied by assessing their ability both to inhibit the binding of 125I-labeled bovine thyrotropin (125I-bTSH) to thyroid membranes and to activate adenylate cyclase therein. Both partially and highly purified hCG preparations inhibited the binding of 125I-bTSH, but hCG-c was approximately 24 times more potent than hCG-p. hCG-c also activated adenylate cyclase in a dose-dependent manner, while hCG-p, in the same concentrations, had no effect. The content of hCG in hCG-c and hCG-p was measured by radioimmuno- and radioreceptor assays, and the results agreed quite closely with those reported by bioassay. Both preparations of hCG inhibited the binding of 125I-bTSH to bovine thyroid membranes in a non-competitive manner, as revealed by Lineweaver-Burk analysis. hCG-c could only partially (60%) displace 125I-bTSH prebound to thyroid membranes; in contrast, unlabeled bTSH displaced 125I-bTSH to a much greater extent (90%). hCG-c preparations may contain a thyroid-stimulating factor distinct from hCG, which interacts with TSH receptors in bovine thyroid membranes in a complex manner. Purified hCG would appear to have little, if any, thyroid-stimulating activity in the bovine system. Since others have presented evidence that purified hCG is a thyroid stimulator in the mouse, it is suggested that there may be important species-related differences in the thyroid responses to hCG, much as is the case with the thyroid-stimulating immunoglobulins in Graves'' disease. In this context, it would remain to be determined whether purified hCG is a significant stimulator of the human thyroid. The effects of several polypeptide hormones other than hCG were also evaluated in the bovine TSH receptor system. Luteinizing hormones (LH) from several species were potent inhibitors of 125I-bTSH binding. Human LH was a better inhibitor than human TSH, while rat LH and rat TSH were approximately equal in potency. Insulin, glucagon and prolactin, as well as human FSH, had no effect. The TSH receptor in bovine thyroid membranes is not completely specific in regard to either species or hormones.