Triiodothyronine-induced Thyrotoxicosis Increases Mononuclear Leukocyte β-Adrenergic Receptor Density in Man

Ann M. Ginsberg; William E. Clutter; Suresh D. Shah; Philip E. Cryer

doi:10.1172/JCI110218

Triiodothyronine-induced Thyrotoxicosis Increases Mononuclear Leukocyte β-Adrenergic Receptor Density in Man

Ann M. Ginsberg, William E. Clutter, Suresh D. Shah, and Philip E. Cryer

Published June 1, 1981 - More info

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Abstract

β-Adrenergic receptors are increased in some tissues of experimentally thyrotoxic animals but are reported to be unchanged in mononuclear leukocytes of spontaneously thyrotoxic humans. We examined the effects of triiodothyronine (100 μg/d for 7 d) and placebo on high-affinity mononuclear leukocyte β-adrenergic receptors in 24 normal human subjects, using a double-blind design. β-Adrenergic receptors were assessed by specific binding of the antagonist (-)[³H]dihydroalprenolol. Triiodothyronine administration resulted in objective evidence of moderate thyrotoxicosis and an increase in mean (-)[³H]dihydroalprenolol binding from 25±3 to 57±9 fmol/mg protein (P < 0.001). The latter was attributable, by Scatchard analysis, to an increase in β-adrenergic receptor density (967 ± 134 to 2250 ± 387 sites per cell, P < 0.01); apparent dissociation constants did not change. Placebo administration had no effects. Marked inter- and intraindividual variation in mononuclear leukocyte β-adrenergic receptor density was also noted. Because this was approximately threefold greater than analytical variation, it is largely attributable to biologic variation. Thus, we conclude: (a) The finding of a triiodothyronine-induced increase in mononuclear leukocyte β-adrenergic receptor density in human mononuclear leukocytes, coupled with similar findings in tissues of experimentally thyrotoxic animals, provides support for the use of mononuclear leukocytes to assess receptor status in man. (b) There is considerable biologic variation in β-adrenergic receptor density in man. (c) The findings of thyroid hormone-induced increments in β-adrenergic receptor density provide a plausible mechanism for the putative enhanced responsiveness to endogenous catecholamines of patients with thyrotoxicosis.