Studies on thyroxine-binding globulin

Bartalena, Luigi

doi:10.1007/bf03348858

Cited by 8 publications

(3 citation statements)

References 142 publications

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“…There are several lines of evidence supporting the validity of the free hormone hypothesis with respect to T 4 : the rate of tissue uptake never exceeds the rate of spontaneous T 4 dissociation from its binding proteins (86); the constant rate of T 4 tissue influx is very high, as would be expected for an uptake that occurs exclusively through the free (very small) fraction of hormone (97); when rat liver is perfused with solutions where T 4 is bound to different proteins (including TTR) in conditions that minimize the re-association of the T 4 that dissociates from the binding proteins, the rate constant of hepatic uptake is similar to the spontaneous dissociation constant of the T 4 -protein complex (98). Other evidence relies on the fact that humans with total or partial TBG deficiency (13,15) 16) remain euthyroid. Similarly, it has been demonstrated that in albumin-deficient rats (87) and in patients with dysalbuminemic hyperthyroxinemia (16) thyroid hormone transfer into the tissues is normal.…”

Section: The Free Hormone Hypothesismentioning

confidence: 97%

Transthyretin as a Thyroid Hormone Carrier: Function Revisited

Palha¹

2002

Clinical Chemistry and Laboratory Medicine

112

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Thyroid hormones are essential for normal mammalian development and for normal metabolism. Thyroxine (T4) is the principal product synthesized by the thyroid follicles, and triiodothyronine (T3), the biologically active hormone, derives mainly from tissue T4 deiodination. More than 99% of the circulating hormone is bound to plasma proteins, mainly to thyroxine-binding globulin, transthyretin and albumin in man, and to transthyretin and albumin in rodents. The role of plasma proteins in the transport of hormones to target tissues has, for a long time, been controversial. The liver and the choroid plexus are the major sites of transthyretin synthesis, tissues from which transthyretin is secreted into the blood and the cerebrospinal fluid, respectively. Transthyretin has been proposed to mediate thyroid hormone transfer into the tissues, particularly into the brain across the choroid-plexus-cerebrospinal fluid barrier. Studies in a transthyretin-null mice strain have shown conclusively that transthyretin is not indespensable for thyroid hormones' entry into the brain and other tissues, nor for the maintenance of an euthyroid status. An euthyroid status is also observed in man totally deprived of thyroxine-binding globulin and in rats without albumin. Taken together, these results exclude dependence of thyroid hormone homeostasis on any major plasma carrier per se. This evidence agrees with the free hormone hypothesis which states that the biologically significant fraction, that is taken up by the tissues, is the free circulating hormone.

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Section: The Free Hormone Hypothesismentioning

confidence: 97%

Transthyretin as a Thyroid Hormone Carrier: Function Revisited

Palha¹

2002

Clinical Chemistry and Laboratory Medicine

112

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“…Thyroxine-binding globulin (TBG), the major thyroid hormone-binding protein, is synthesized and secreted by the liver (81). The human TBG gene has been shown to have a high degree of homology with the two plasma serine protease inhibitors (SERPINS) aj-antichymotrypsin (ACT, 58%) and aj-antitrypsin (AT, 53%) (82). Although the significance of this homology is unclear, the SERPIN structure of TBG might play a role in the targeted delivery of thyroid hormones (83).…”

Section: Studies In Vivomentioning

confidence: 99%

Interleukin-6 and the thyroid

Bartalena

Brogioni

Grasso

et al. 1995

European Journal of Endocrinology

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“…TBG is the major thyroid hormone carrier in man. There are cases of humans with partial or total TBG deficiency, which results in euthyroid hypothyroxinemia (Refetoff 1989, Bartalena 1993. Even though exposure to cold is known to induce alteration in thyroid hormone metabolism in humans (Solter et al 1989, Sawhney et al 1995, Do et al 2004, to the best of our knowledge there are no reports on the ability of these individuals to adapt to cold.…”

Section: Figurementioning

confidence: 99%

Transthyretin is not necessary for thyroid hormone metabolism in conditions of increased hormone demand

Sousa¹,

Escobar²,

Oliveira³

et al. 2005

Journal of Endocrinology

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Thyroid hormones circulate in blood mainly bound to plasma proteins. Transthyretin is the major thyroxine plasma carrier in mice. Studies in transthyretin-null mice revealed that the absence of transthyretin results in euthyroid hypothyroxinemia and normal thyroid hormone tissue distribution, with the exception of the choroid plexus in the brain. Therefore, transthyretin does not influence normal thyroid hormone homeostasis under standard laboratory conditions. To investigate if transthyretin has a buffer/storage role we challenged transthyretin-null and wild-type mice with conditions of increased hormone demand: (i) exposure to cold, which elicits thermogenesis, a process that requires thyroid hormones; and (ii) thyroidectomy, which abolishes thyroid hormone synthesis and secretion and induces severe hypothyroidism. Transthyretin-null mice responded as the wild-type both to changes induced by stressful events, namely in body weight, food intake and thyroid hormone tissue content, and in the mRNA levels of genes whose expression is altered in such conditions. These results clearly exclude a role for transthyretin in thyroid hormone homeostasis even under conditions of increased hormone demand.

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Studies on thyroxine-binding globulin

Cited by 8 publications

References 142 publications

Transthyretin as a Thyroid Hormone Carrier: Function Revisited

Transthyretin as a Thyroid Hormone Carrier: Function Revisited

Interleukin-6 and the thyroid

Transthyretin is not necessary for thyroid hormone metabolism in conditions of increased hormone demand

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