Evidence for thyroid hormone as a positive regulator of serum thyrotropin bioactivity

Context: The regulation of TSH bioactivity in humans is not completely understood. Objective: The aim of the study was to investigate the role of serum thyroid hormones in regulating the bioactivity of TSH. Design: We determined in vitro TSH bioactivity and glycosylation in nine patients (six females and three males, age 41.3 yr) with primary hypothyroidism before and after L-T-4 replacement, in 11 age- and sex-comparable controls (seven females and four males, age 37.6 yr), and in two thyroidectomized patients with TSH-secreting adenomas during and after L-T4 withdrawal. Methods: In vitro TSH bioactivity was measured by a sensitive and specific bioassay based on cAMP generation by Chinese hamster ovary cells transfected with human TSH receptor. TSH glycosylation was assessed by concanavalin A lectin and ricin column affinity chromatography. Results: In vitro TSH bioactivity in hypothyroid patients was low as compared with controls (0.48 +/- 0.1 vs. 1.1 +/- 0.2; P = 0.004) and increased during L-T-4 (0.48 +/- 0.1 vs. 0.8 +/- 0.1; P = 0.01). A strong significant correlation (r = + 0.80; P = 0.004, Spearman) was observed between the absolute increments of serum TSH bioactivity and T-3 during L-T-4 replacement. The degree of sialylation was elevated in hypothyroid patients before treatment (47 +/- 2.4% vs. 29 +/- 4.3%; P = 0.002) and decreased significantly after L-T4 (47 +/- 2.4% vs. 33 +/- 4.3%; P = 0.02). The mannose content of serum TSH in hypothyroid patients was similar to controls and did not change during L- T-4. In vitro TSH bioactivity also decreased in patients with TSH-secreting adenomas during L-T-4 withdrawal. Conclusion: These data indicate that serum thyroid hormone level is a positive regulator of TSH bioactivity.