Heterogeneous Forms of Thyroid-Stimulating Hormone in Mouse Thyrotropic Tumor and Serum: Differences in Receptor-Binding and Adenylate Cyclase-Stimulating Activity

Summary

Thyroid-stimulating hormone (TSH) in tumor and serum of mice with thyrotropic tumors was studied by radioimmunoassay (RIA), radioreceptor assay (RRA) and thyroid adenylate cyclase assay (ACA). In unfractionated samples, serum TSH displayed significantly higher ACA/RIA (0.69 ± 0.10) and ACA/RRA ratios (0.79 ± 0.04) than TSH in tumor extracts (0.45 ± 0.05 and 0.31 ± 0.01, respectively). After gel chromatography, both tumor and serum TSH activity measured in RIA and RRA eluted in broad, heterogeneous peaks with an apparent molecular weight range of 26,000-44,000 daltons. The ACA activity of tumor TSH eluted in 2 sharp peaks (26,000 and 44,000) while that of serum TSH eluted in 3 peaks (26,000, 33,000 and 44,000). The ACA/RIA and ACA/RRA ratios varied greatly among the chromatography fractions, the lowest ratios being detected in the tumor TSH of 33,000 daltons (0.02 for each) and the highest ratios in both tumor and serum TSH of 26,000 (ACA/RIA = 1.60-1.90, ACA/RRA = 1.12-1.20). Since previous biosynthetic studies have suggested that such heterogeneous forms of mouse tumor TSH differ solely in carbohydrate content, our data suggest that the biologic activity of TSH may be modulated by its glycosylation.

Key-Words:

Adenylate Cyclase Assay - Radioimmunoassay - Radioreceptor Assay - Thyrotropic Tumor - TSH