Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to examine the interaction of phosphonoformic acid (PFA) with the Na(+)-sulfate cotransporter and the effect of thyroid hormone (triiodothyronine; T3) on Na(+)-dependent sulfate transport and Na(+)-dependent PFA binding in mouse renal brush-border membrane vesicles. PFA inhibits Na(+)-dependent sulfate transport in a competitive manner [apparent inhibitory constant (Ki) = 4.3 +/- 1.1 mM]. T3 administered in pharmacological doses significantly stimulates Na(+)-dependent sulfate transport in renal brush-border membranes compared with vehicle-treated controls. Although T3 has no effect on Na(+)-dependent glucose transport, T3 also stimulates Na(+)-dependent phosphate transport. Kinetic studies demonstrate that T3 increases the apparent maximal velocity (Vmax) for Na(+)-sulfate cotransport without changing the apparent Michaelis constant (Km). T3 does not significantly affect either Na(+)-dependent PFA binding or the phosphate- and sulfate-displaceable components of Na(+)-dependent PFA binding. Finally, Na(+)-dependent brush-border membrane sulfate transport is unchanged in phosphate-deprived mice that exhibit increased Na(+)-phosphate cotransport and in X-linked Hyp mice that exhibit impaired Na(+)-phosphate cotransport. The present results demonstrate that 1) PFA is a competitive inhibitor of Na(+)-sulfate cotransport, 2) T3 stimulates Na(+)-dependent sulfate, as well as Na(+)-dependent phosphate transport, but has no effect on PFA binding, and 3) phosphate deprivation and the X-linked Hyp mutation do not influence Na(+)-sulfate cotransport.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal brush-border membrane Na(+)-sulfate cotransport: stimulation by thyroid hormone. 183 65

Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentration were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.
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PMID:Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins. 678 95

We examined the results of the Northwest Regional Screening Program from May 1975 to June 1991 to determine the prevalence of inherited thyroxine-binding globulin (TBG) deficiency and its effect on thyroid hormone concentrations in infants. Serum thyroxine (T4), triiodothyronine resin uptake (T3RU), and thyrotropin values were requested of physicians caring for all infants with a single filter paper T4 level < 38.6 nmol/L (3 micrograms/dl) or a T4 level < 3rd percentile on two filter paper tests (at birth and 2 to 6 weeks of age). From 1,367,724 infants screened in five states, TBG deficiency, an X-linked disorder, was identified in 317 infants (285 boys). For the entire screening program the calculated frequency of TBG deficiency was 1:4315 infants (1:2400 for boys). In Oregon, where 95% of infants have two screening tests performed, the calculated frequency was somewhat higher (1:3080 infants; 1712 boys) and is probably more accurate. The mean serum T4 concentration for TBG-deficient boys was 41.9 nmol/L (3.26 micrograms/dl); 31% had values < 25.7 nmol/L (2.0 micrograms/dl). The mean serum T4 concentration for TBG-deficient girls was 60.2 nmol/L (4.68 micrograms/dl), with none < 2.0 micrograms/dl. The mean T3RU value was 0.472 in TBG-deficient boys, and 0.412 in TBG-deficient girls; the T3RU value was > 0.55 in 24% of TBG-deficient boys but was > 0.55 in only one girl. Free serum T4 levels were normal in all 56 TBG-deficient infants studied, and TBG levels were low in all 20 infants studied. Inherited TBG deficiency is common in boys in the Northwest, with a frequency of 1:1700 and a male/female ratio of 8.9:1. Boys with TBG deficiency have mild, moderate, or severe alterations in total T4 and T3RU values, but severe deficiency is rare in girls.
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PMID:Thyroxine-binding globulin deficiency detected by newborn screening. 834 39

1. Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (<3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2. This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3. Serum T4 and T3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4. The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.
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PMID:Effect of propylthiouracil-induced hypothyroidism on the onset of skeletal muscle necrosis in dystrophin-deficient mdx mice. 966 89

T4-binding globulin (TBG) is the major thyroid hormone transport protein in human serum. Inherited TBG abnormalities do not usually alter the metabolic status and are transmitted in X-linked inheritance. A high prevalence of complete TBG deficiency (TBG-CD) has been reported among the Bedouin population in the Negev (southern Israel). In this study we report a novel single mutation causing complete TBG deficiency due to a deletion of the last base of codon 38 (exon 1), which led to a frame shift resulting in a premature stop at codon 51 and a presumed truncated peptide of 50 residues. This new variant of TBG (TBG-CD-Negev) was found among all of the patients studied. We conclude that a single mutation may account for TBG deficiency among the Bedouins in the Negev. This report is the first to describe a mutation in a population with an unusually high prevalence of TBG-CD.
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PMID:A novel mutation causing complete thyroxine-binding globulin deficiency (TBG-CD-Negev) among the Bedouins in southern Israel. 1106 24

Kallmann syndrome is a very rare hereditary disease. It is characterized by hypogonadotropic hypogonadism in association with anosmia ot hyposmia, both of which occur as a result of the failure of neuronal migration of the luteinizing hormone releasing hormone (LHRH)--secreting neurons and the neurons of the vemeronasal nerve. It can be autosomal dominant, autosomal recessive, or X-linked mode of inheritance. We report a case of Kallmann syndrome that presented with delay puberty, color blindness, gynecomastia, and absence of smell. Plasma levels of LH, FSH and testosterone were very low. The patient's adrenal and thyroid hormone levels were normal. Chromosome analysis showed 46, XY karyotype without deletion in KAL gene (Xp22.3) from FISH. After 9 months of treatment by HCG and HMG, the amount of pubic hair and the volume of bilateral testes, as well as the level of testosterone had increased. Most importantly, motile sperm count be found in semen.
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PMID:Kallmann syndrome--a case report. 1238 Mar 26

Thyroxin (T4) binding globulin (TBG) the major thyroid hormone transport protein in humans. Congenital or acquired problems lead to TBG excess. Inheritance of TBG excess follows an X-linked pattern. A 21-month-old boy with ichthyosis was referred to the Pediatric Endocrinology Clinic with high levels of thyroid hormones (TT3 = 325 ng/dl, TT4 23 microg/dl, FT3 = 3.49 pg/dl, FT4 = 1.44 ng/dl, TSH = 2.48 microIU/ml). He was clinically euthyroidic. Thyroid gland was normal in size and homogeneous. Thyroid autoantibodies were negative. TSH responded normally to thyroid releasing hormone (TRH) stimulus. TBG was elevated (56 microg/ml). Family investigation revealed high levels of TBG in mother grandfather, and an uncle. To our knowledge, no other TBG excess with ichthyosis has been reported in the literature.
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PMID:Familial thyroxin-binding globulin excess with ichthyosis: a case report. 1521 50

Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transporter, the gene of which is located on the X chromosome. We tested whether mutations in MCT8 cause severe psychomotor retardation and high serum triiodothyronine (T3) concentrations in five unrelated young boys. The coding sequence of MCT8 was analysed by PCR and direct sequencing of its six exons. In two patients, gene deletions of 2.4 kb and 24 kb were recorded and in three patients missense mutations Ala150Val, Arg171 stop, and Leu397Pro were identified. We suggest that this novel syndrome of X-linked psychomotor retardation is due to a defect in T3 entry into neurons through MCT8, resulting in impaired T3 action and metabolism.
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PMID:Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. 1548 19

Recent genetic analysis in several patients presenting a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels have revealed mutations or deletions in the gene of the monocarboxylate transporter 8 (MCT8). Because in vitro MCT8 functions as a TH transporter, the complex clinical picture of these patients indicated an important role for MCT8 in TH-dependent processes of brain development. To provide a clue to the cellular function of MCT8 in brain, we studied the expression of MCT8 mRNA in the murine central nervous system by in situ hybridization histochemistry. In addition to the choroid plexus structures, the highest transcript levels were found in neo- and allocortical regions (e.g. olfactory bulb, cerebral cortex, hippocampus, and amygdala), moderate signal intensities in striatum and cerebellum, and low levels in a few neuroendocrine nuclei. Colocalization studies revealed that MCT8 is predominantly expressed in neurons. Together with the spatiotemporal expression pattern of MCT8 during the perinatal period, these results strongly indicate that MCT8 plays an important role for proper central nervous system development by transporting TH into neurons as its main target cells.
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PMID:The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations. 1576 1

Thyroid hormone is important for development of various tissues, in particular brain, and for regulation of metabolic processes throughout life. The follicular cells of the thyroid gland produce predominantly T4 (thyroxine), but the biological activity of thyroid hormone is largely exerted by T3 (3,3',5-tri-iodothyronine). The deiodinases involved in T4-to-T3 conversion or T4 and T3 degradation, as well as the T3 receptors, are located intracellularly. Therefore the action and metabolism of thyroid hormone require transport of iodothyronines across the cell membrane via specific transporters. Recently, a number of transporters capable of cellular uptake of iodothyronines have been identified. The most specific transporters identified so far are OATP1C1 and MCT8, which appear to be involved in T4 transport across the blood-brain barrier, and in T3 transport into brain neurons, respectively. The MCT8 gene is located on human chromosome Xq13, and mutations in MCT8 are associated with X-linked severe psychomotor retardation and elevated serum T3 levels.
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PMID:Thyroid hormone transporters. 1566 14


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