Properties of human thyroidal and extrathyroidal TSH receptors

Abstract

The presence of high affinity receptor sites for TSH in the human is not limited to the thyroid gland. The properties of thyroidal and extrathyroidal TSH binding were explored through the effect of various agents (TSI [thyroid stimulating Ig] of Graves'' disease, propranolol, hCG [human chorionic gonadotropin], N-acetylneuraminic acid, ACTH, insulin and L-thyroxine) on the receptors. Statistically significant inhibition of [125I]TSH binding occurred with all Ig TSI of Graves'' disease on thyroid cell membrane receptors. Thirty-three per cent of the same Ig showed significant inhibition of [125I]TSH binding when testicular cell membranes were used, while there was no such inhibition when renal cell membranes were utilized. D or L-propranolol at least doubled the [125I]TSH initial binding to the thyroid membranes but had no effect on the testicular or fat cell binding. hCG at concentrations of 400 USP units/350 .mu.l totally inhibited the [125I]TSH from binding to testicular membranes but not to thyroid or fat cell membranes. Conversely, the binding of [125I]hCG to human testicular membrane was inhibited by both stable hCG and TSH, but with human thyroid membrane, only TSH could inhibit binding of [125I]hCG. The TSH receptors in extrathyroidal tissues may not be identical to TSH receptors within the thyroid. TSH binding to thyroidal tissue was significantly suppressed by N-acetylneuraminic acid, was increased by D and L-propranolol and was unaffected by ACTH and insulin. L-thyroxine had a dose-related suppressive effect on the TSH binding, commencing at 50 .mu.g/ml. These effects were observed in vitro, but some of the above agents may also interfere with thyroid gland function in vivo. A number of interactions may take place at the TSH binding sites which could alter TSH binding and/or function.