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

Abstract

The regulation of TSH bioactivity in humans is not completely understood. The aim of the study was to investigate the role of serum thyroid hormones in regulating the bioactivity of TSH. 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-T(4) withdrawal. 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. 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-T(4) (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. These data indicate that serum thyroid hormone level is a positive regulator of TSH bioactivity.