Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs

Franklyn, Jayne A.; King, S.S.; Ahlquist, James; Sheppard, M. C.

doi:10.1530/acta.0.1210383

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…The regulatory properties of mouse TBG and TTR, either as concerns the modulation of their serum activities by NEFAs or the control of their synthesis by the thyroid status, are in many respects similar to those recently demonstrated in the rat [7][8][9][10] or to the available observations in man [27,33]. Among the evidenced analogies are the inhibition of TBG activity by oleic acid and the up-regulation of TBG in hypothyroid states (whether after PTU treatment or during physiological hypothyroidism of neonatal animals), contrasting with the non-response of TTR to hypothyroidism [7,34].…”

Section: Discussionsupporting

confidence: 82%

Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse

Vranckx

Savu

Maya

et al. 1990

Biochemical Journal

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We confirm our finding of a major development-regulated thyroxine-binding globulin (TBG) in the serum of the euthyroid mouse and investigate a number of its binding, structural and regulatory properties. Between 16 days foetal and 60 days postnatal life, the thyroxine (T4)- and tri-iodothyronine (T3)-binding activities of the sera show a striking ontogenic pattern: the binding is 2-3 times higher in foetuses than in mothers, then further increases after birth, reaching between 3 and 5 days maximum values which are 7-8 times higher than the adult ones. This pattern is not correlated with the ontogenesis of the acknowledged specific (transthyretin, TTR) and non-specific (albumin, alpha 1-foetoprotein) thyroid-hormone carriers of the mouse sera. PAGE studies demonstrate that the protein responsible for the elevated binding of the perinatal period is an alpha 1-globulin, with a migration similar to that of human and rat TBGs. Scatchard analysis is consistent with the notions that the T4-binding sites of TBG have high association constants, about two orders of magnitude above the T4 sites of TTR (10(9) M-1 as against 10(7) M-1) and low capacities (37 and 4 nmol/g of serum proteins in pups and adults respectively). Isoelectric focusing (i.e.f.) demonstrates that mouse TBG is a microheterogeneous protein separable, as a function of the pH gradient, in up to 10-12 isoforms, Marked shifts of the relative abundance of isoforms in the course of development are evidenced. The modulation of the TBG binding activity by non-esterified fatty acids (NEFA) and the control of its synthesis by the thyroid status are also reported. Mono- and poly-unsaturated NEFAs are strong inhibitors of the TBG, although they affect TTR less readily. On the other hand, the biosynthesis and/or secretion of TBG, but not of TTR, is under thyroid-hormone control, experimental hypothyroidism inducing a marked increase of the serum TBG. The TBG of mouse behaves as a highly significant parameter of development, pointing to a likely important function of the protein in the process of maturation. Our finding of major TBGs in both euthyroid rats and mice suggests that TBG is more widely spread than was thought until now, but difficult to detect in certain species outside definite maturation stages.

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Section: Discussionsupporting

confidence: 82%

Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse

Vranckx

Savu

Maya

et al. 1990

Biochemical Journal

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“…Previous studies demonstrated a tremendous induction of S14 by thyroid hormone in animal. [ 1 , 2 , 6 ] Our results suggested the effects of thyroid hormone on serum S14 levels in human.…”

Section: Discussionsupporting

confidence: 50%

“…[ 10 ] Thyroid hormone was demonstrated to upregulate S14 gene expression in the rat liver. [ 1 , 2 ] In this study, we successfully developed a competitive ELISA system to measure serum S14 levels in human subjects. Our study is the first to investigate the serum S14 levels in humans and the effect of thyroid function status on serum S14 level.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, S14 mRNA was increased in a dose-dependent manner with triiodothyronine (T3) treatment in these hypothyroid animals. [ 2 ] The experiments with the hypothyroid rats injected with T3 demonstrated a swift induction of hepatic S14 mRNA within 20 minutes of treatment. [ 3 ] This is the most rapid effect of T3 on hepatic gene expression documented to date.…”

Section: Introductionmentioning

confidence: 99%

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Serum Spot 14 concentration is negatively associated with thyroid-stimulating hormone level

et al. 2016

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Spot 14 (S14) is a protein involved in fatty acid synthesis and was shown to be induced by thyroid hormone in rat liver. However, the presence of S14 in human serum and its relations with thyroid function status have not been investigated.The objectives of this study were to compare serum S14 concentrations in patients with hyperthyroidism or euthyroidism and to evaluate the associations between serum S14 and free thyroxine (fT4) or thyroid-stimulating hormone (TSH) levels.We set up an immunoassay for human serum S14 concentrations and compared its levels between hyperthyroid and euthyroid subjects. Twenty-six hyperthyroid patients and 29 euthyroid individuals were recruited. Data of all patients were pooled for the analysis of the associations between the levels of S14 and fT4, TSH, or quartile of TSH.The hyperthyroid patients had significantly higher serum S14 levels than the euthyroid subjects (median [Q1, Q3]: 975 [669, 1612] ng/mL vs 436 [347, 638] ng/mL, P < 0.001). In univariate linear regression, the log-transformed S14 level (logS14) was positively associated with fT4 but negatively associated with creatinine (Cre), total cholesterol (T-C), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and TSH. The positive associations between logS14 and fT4 and the negative associations between logS14 and Cre, TG, T-C, or TSH remained significant after adjustment with sex and age. These associations were prominent in females but not in males. The logS14 levels were negatively associated with the TSH levels grouped by quartile (ß = −0.3020, P < 0.001). The association between logS14 and TSH quartile persisted after adjustment with sex and age (ß = −0.2828, P = 0.001). In stepwise multivariate regression analysis, only TSH grouped by quartile remained significantly associated with logS14 level.We developed an ELISA to measure serum S14 levels in human. Female patients with hyperthyroidism had higher serum S14 levels than the female subjects with euthyroidism. The serum logS14 concentrations were negatively associated with TSH levels. Changes of serum S14 level in the whole thyroid function spectrum deserve further investigation.

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“…It was first identified in 1982 as a result of its marked and rapid induction by thyroid hormone (Seelig et al, 1982). The multilayered regulation and nuclear localization of Thrsp led researchers to believe that it plays a role in tissue-specific control of metabolism in response to changing dietary and hormonal factors (Campbell et al, 2003;Cunningham et al, 1998;Franklyn et al, 1989). Thrsp has been reported to be a homodimeric transcriptional activator that serves as a component of a tripartite complex with a 36 kDa hepatic protein in rat liver to modulate gene expression (Cunningham et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Expression, purification and preliminary crystallographic analysis of human thyroid hormone responsive protein

et al. 2011

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Thyroid hormone responsive protein (Thrsp, also known as Spot 14 and S14) is a carbohydrate-inducible and thyroid-hormone-inducible nuclear protein specific to liver, adipose and lactating mammary tissues. Thrsp functions to activate genes encoding fatty-acid synthesis enzymes. Recent studies have shown that in some cancers human Thrsp (hS14) localizes to the nucleus and is amplified, suggesting that it plays a role in the regulation of lipogenic enzymes during tumourigenesis. Thrsp, a member of the Spot 14 superfamily, is an acidic homodimeric protein with no sequence similarity to other mammalian gene products and its biochemical function is elusive. To shed light on the structure-function relationship of this protein, human Thrsp was crystallized. Recombinant human Thrsp (hThrsp), the N-terminally truncated human Thrsp 10-146 (hThrsp9) and their selenomethionyl (SeMet) derivatives were expressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. Diffraction-quality crystals were grown at 293 K using Li 2 SO 4 as a precipitant. Using synchrotron radiation, data for the hThrsp SeMet derivative, hThrsp9 and its SeMet derivative were collected to 4.0, 3.0 and 3.6 Å resolution, respectively, at 100 K. The crystals of full-length hThrsp and its SeMet derivative belonged to space group P4 1 2 1 2, with approximate unit-cell parameters a = b = 123.9, c = 242.1 Å , = = = 90.0 . In contrast, the crystals of the truncated hThrsp9 and its SeMet derivative belonged to space group P2 1 2 1 2 1 , with approximate unit-cell parameters a = 91.6, b = 100.8, c = 193.7 Å , = = = 90.0 . A molecular-replacement solution calculated using a murine Spot 14 structure as a search model indicated the presence of six molecules per asymmetric unit, comprising three hThrsp homodimers.

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Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs

Cited by 8 publications

References 15 publications

Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse

Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse

Serum Spot 14 concentration is negatively associated with thyroid-stimulating hormone level

Expression, purification and preliminary crystallographic analysis of human thyroid hormone responsive protein

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