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Evidence for Thyroid Hormone as a Positive Regulator of Serum Thyrotropin Bioactivity

Neuroendocrine Unit, Endocrine Division, Universidade Federal de São Paulo, São Paulo, SP 04039-002, Brazil

Address all correspondence and requests for reprints to: Julio Abucham, M.D., Ph.D., Neuroendocrine Unit, Endocrinology Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo, 910. São Paulo 04039-002, Brazil. E-mail: julioabucham{at}nw.com.br.

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-T₄ 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-T₄ (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 T₃ during L-T₄ 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-T₄. In vitro TSH bioactivity also decreased in patients with TSH-secreting adenomas during L-T₄ withdrawal.

Conclusion: These data indicate that serum thyroid hormone level is a positive regulator of TSH bioactivity.