Thyroid hormone binding to human serum prealbumin and rat liver nuclear receptor: kinetics, contribution of the hormone phenolic hydroxyl group, and accommodation of hormone side-chain bulk

Abstract

The kinetics of binding of the thyroid hormones, L-thyroxine (L-T,) and ~-3,5,3'-triiodothyronine (L-T~), to human serum prealbumin were measured by a rapid gel filtration procedure to separate protein-bound from free hormone. The association rate constant for the ~-T,-prealbumin complex is comparable in magnitude to that of the ~-T~-r eceptor complex. A lower limit for the ~-T~-prealbumin association rate constant is lo6 M-' min-'. The dissociation rate constant for the ~-T,-prealburnin complex is higher than that for the ~-T,-prealbumin complex. This is attributed to steric effects, due to the extra iodine atom of L-T,, that are operative in L-T, dissociation from prealbumin. The dissociation rate constant for the ~-T,-prealbumin complex is much higher than that for the ~-T~-receptor complex, implying that the receptor binding site is in some sense more confined than the binding site of prealbumin.

Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein

“…In our previous work, several biphenyl thyroid hormone analogs were shown to bind strongly to TTR, supporting the importance of the linear biphenyl system in interacting with the specific binding domain of the protein. Consistent with the suggestion of others (Somack et al, 1982), our previous molecular modeling studies (Rickenbacher et al, 1986;McKinney et al, 1987) indicated that para hydroxylation was not necessarily required for binding and that a chlorine atom could reasonably replace the hydroxyl group. Molecular modeling and energy calculations have also been used in our previous work (Pedersen et al, 1986) to assess the binding mode and torsional angle (about PCB pivot bond) requirements for PCB binding to TTR.…”

“…A modification of the gel filtration binding assay described by Somack et al (1982) , and competitors (cold T 4 or PCBs) with increasing concentrations (1 to 1000 nM). The final volume of the assay mixture was 0.5 ml.…”

Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins

“…Human TTR (98% purity) and human TBG (99.9% purity) were obtained from Calbiochem (San Diego, CA, USA). Molecular weight of 55 kDa and 58 kDa is used, respectively, to calculate the molar concentration of TTR and TBG according to the literature (Hocman, 1981;Somack et al, 1982). Fluorescence probe 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANSA) was purchased from Sigma-Aldrich Co. (St Louis, MO, USA).…”

Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells.

“…Antagonists have been described that interact with the mineralocorticoid, glucocorticoid, estrogen, and progesterone receptors (1). It is surprising, however, despite extensive structure activity studies conducted over the past 20 years (2,3), no antagonist for thyroid hormone receptor action has been identified.…”