Assessment of Urinary Thyrotropin-Competing Activity in Choriocarcinoma and Thyroid Disease: Further Evidence for Human Chorionic Gonadotropin Interacting at the Thyroid Cell Membrane

Abstract

The TSH-competing activity of kaolin-acetone urine concentrates from patients with choriocarcinoma and/or thyroid dysfunction was investigated using a highly sensitive TSH radioligand-receptor assay which employs porcine thyroid homogenate and membrane-purified [¹²⁵I]bovine TSH. TSHcompeting activity in urine concentrates obtained from normal pregnant women and patients with hyperthyroid Graves' disease or primary and secondary hypothyroidism did not exceed that found in urinary concentrates from normal control subjects. Euthyroid patients with choriocarcinoma, whose urinary hCG levels were typical of those found in pregnancy (2.3-73 εg/ml), had levels of urinary TSH-competing activity indistinguishable from those of normal controls. In contrast, increased urinary TSH-competing activity was readily detected in urine extracts from four choriocarcinoma patients with high urinary hCG levels (620-5,200 εg/ml). Three of these four patients were biochemically hyperthyroid and their urine concentrates demonstrated thyroid-stimulating activity, as measured in the mouse thyroid bioassay. Furthermore, a reduction in tumor activity after chemotherapy led to a concomitant reduction in urinary TSH-competing activity, hCG, and thyroid-stimulating activity. Both crude and purified hCG preparations obtained from pooled pregnancy urine exhibited TSH-competing activity in direct proportion to their hCG content, as determined by hCG radioreceptor assay. The crude and purified hCG also exhibited significant TSH-competing activity at concentrations (500-10,000 εg/ml hCG) similar to those found in the urinary concentrates of the patients with choriocarcinoma. There was no evidence of a factor other than hCG as the cause of the TSH-competing activity in the crude or purified hCG preparations or in the urine of hyperthyroid patients with choriocarcinoma. These data suggest that the substance with TSH-competing activity in urinary concentrates from patients with metastatic choriocarcinoma is hCG itself and constitute additional evidence for the view that hCG is the abnormal thyroid stimulator in choriocarcinoma-associated hyperthyroidism. Furthermore, hCG appears to interact with the thyroid cell membrane at or close to the TSH receptorbinding site.