Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormone exerts its biological effect by binding to a TR. Both liganded and unliganded TRs regulate the transcription of T(3)-responsive genes. Cofactors with activating or repressing function modulate the transcriptional regulation by TRs. We showed that steroid receptor coactivator 1 (SRC-1)-deficient mice (SRC-1(-/-)) exhibit partial resistance to thyroid hormone at the level of the pituitary thyrotrophs. To determine whether SRC-1 deficiency affects globally T(3)-dependent transcriptional regulation, we studied the effects of thyroid hormone deprivation and replacement on the expression of several genes in different tissues of SRC-1(-/-) and wild-type mice (SRC-1(+/+)). Thyroid hormone deficiency was induced by a low iodine diet (LoI) supplemented with propylthiouracil (PTU) for 2 wk. L-T(3) was injected ip for the last 4 d in one group (PTU+T(3) group), and another group (PTU group) received only vehicle. Levels of mRNAs for T(3)-responsive genes were determined by Northern blotting: GH and TSH beta in pituitary; type 1 iodothyronine 5'-deiodinase, spot 14 (S14), and malic enzyme in liver; and sarcoplasmic reticulum calcium adenosine triphosphatase 2 and myosin heavy chain alpha and beta in heart. Serum parameters, TSH, total cholesterol, creatine kinase, and alkaline phosphatase (AP), were also measured. Hypothyroidism produced a comparable increase in TSH beta mRNA in both genotypes, but its suppression by L-T(3) was attenuated in SRC-1(-/-) mice. In contrast, hypothyroidism failed to reduce S14 mRNA levels in SRC-1(-/-) mice. As a consequence, the response to L-T(3) was not observed in these mice. SRC-1 deficiency had no effect on the expression of the rest of the T(3)-responsive genes examined. Of the four serum parameters, the T(3)-mediated decrease in TSH and changes in AP were attenuated in SRC-1(-/-) mice. We conclude that SRC-1 deficiency altered the expression of only some of the T(3)-responsive genes. SRC-1 appears to be involved not only in transcriptional activation by liganded TRs, but also in the suppression by liganded or unliganded TRs. Some of the effects of SRC-1 may be TR isoform specific.
 ...
PMID:Steroid receptor coactivator-1 deficiency causes variable alterations in the modulation of T(3)-regulated transcription of genes in vivo. 1189 91

Cultured thyroid epithelial cells can be induced to express intercellular adhesion molecule-1 (ICAM-1, or CD54). However, constitutive follicular expression of ICAM-1 has been reported only in thyroid autoimmunity. We evaluated the expression of ICAM-1 mRNA and protein on thyroid tissue from different autoimmune thyroid diseases, and its relationship with other immunologically relevant surface markers, namely costimulatory molecules of B7 family. Thyroid tissue sections were obtained by surgically removed thyroid glands from 6 patients with Hashimoto's thyroiditis (HT), 6 with Graves' disease (GD) and 3 with multinodular nontoxic goiter. We used in situ hybridization to localize ICAM-1 mRNA, and immunohistochemical analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) method. We showed a clear hybridization pattern, localized in follicular cells, in sections of glands with HT. The hybridization pattern was far less pronounced in GD: no staining was apparent on follicular cells. These results were strictly consistent with those obtained by means of immunohistochemistry. Moreover, double-staining experiments demonstrated colocalization of ICAM-1 and B7.1 molecules in HT, whereas no B7.1 expression was observed in Graves' or in non-autoimmune thyroid diseases. These data agree with the hypothesis of distinct immunoregulatory phenomena and effector mechanisms in the 2 main autoimmune thyroid diseases.
 ...
PMID:Different intrathyroid expression of intercellular adhesion molecule-1 (ICAM-1) in Hashimoto's thyroiditis and Graves' disease: analysis at mRNA level and association with B7.1 costimulatory molecule. 1193 73

We report on a 6.5-year-old girl with a balanced translocation between the short arms of chromosomes 1 and 6. She was referred for genetics evaluation because of developmental speech delay and congenital absence of several deciduous and permanent teeth. She was very sensitive to noise (hyperacusis), had poor hair and nail growth, decreased sweating, and turned very red with high fever. She had microcephaly (head circumference at the second centile; weight and height were at 25th centile), short palpebral fissures, epicanthal folds, sparse eyelashes, large ears, partial anodontia, short finger and toenails, and dry skin. She had mild developmental delay. Family history was significant for learning problems in two paternal uncles, one paternal aunt, and several paternal cousins. Thyroid studies, calcium, phosphorus, and alkaline phosphatase levels were normal. Her karyotype was 46,XX,t(1;6)(p22.1;p22.2), and parental karyotypes were normal. This apparently balanced translocation may have resulted in either a submicroscopic loss or disruption of a gene or genes involved in ectodermal dysplasia. There are no reported cases of ectodermal dysplasia associated with this chromosome rearrangement.
 ...
PMID:Child with De Novo t(1;6)(p22.1;p22.1) translocation and features of ectodermal dysplasia with hypodontia and developmental delay. 1260 48

Thyroid hormones exert a profound effect on development, growth, and metabolism of skeleton. In the present study, we evaluated the effects of thyroxine (T4) and growth hormone (GH) on the terminal differentiation of rib growth plate chondrocytes in three-dimensional pellet culture. T4 (30ng/ml) stimulated the expressions of type II and X collagens, alkaline phosphatase (ALP) activity. On the other hand, the expression of chondrogenic transcription factor Sox9 in the T4 treatment group decreased significantly compared to the control group. T4 downregulates Sox9 and promotes hypertrophy. After day 7, T4 increases dramatically the synthesis of type X collagen mRNA, ALP activity, and cellular hypertrophy. Addition of GH does not modify the action of T4. Thus, T4 acts directly on chondrocytes. In conclusion, we demonstrated that T4 enhances the cellular and molecular events of terminal differentiation and hypertrophy of chondrocytes in the three-dimensional cultures.
 ...
PMID:Thyroxine downregulates Sox9 and promotes chondrocyte hypertrophy. 1278 86

The purpose of the present study was to determine the effects of supraphysiologic doses of triiodothyronine (T(3)) on skeletal metabolism, calcium balance, and the calciotropic hormones. Seven healthy, lean men were studied in an inpatient metabolic unit over a 63-day period. All volunteers received oral T(3) at doses of 50-75 microg/d. There was a prompt and sustained increase in calciuria and an overall net negative calcium balance. The pattern of changes in serum osteocalcin, urinary deoxypyridinoline (DPD)/creatinine ratio, and serum bone-specific alkaline phosphatase indicated an early increase in bone resorption followed by a late, incomplete compensatory increase in bone formation. Cumulative net calcium loss was 18.5 +/- 5.4 g over the 63-day treatment period, averaging 218.5 +/- 41.4 mg/d. This represents 0.22% +/- 0.075% of the total skeletal calcium content. The cumulative net calcium loss over the 63-day treatment period was highly correlated with the change in DPD (r = -0.95, p = 0.001). Prompt increases in corrected serum calcium values resulted in serum intact parathyroid hormone (iPTH) levels decreasing by 30.4% (p = 0.08). Bone mineral density showed no change. We conclude that T(3) accelerates bone turnover and that bone formation does not increase acutely to prevent bone loss.
Thyroid 2003 Apr
PMID:The effects of triiodothyronine on bone metabolism in healthy ambulatory men. 1280 4

This experimental study was designed to examine the effects of hyperthyroidism on osteoporotic cytokines such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in the physiological concentrations and in the deficiency of estrogen. We investigated the effects of thyroid hormones on cytokines and bone metabolism in L-thyroxine induced ovary-intact and ovariectomised rats, as levels of cytokines were increased in hyperthyroidism. The rats were divided into three groups. In the first group, L-thyroxine-induced hyperthyroid rats were ovariectomised (OVX), while the OVX rats were administered L-thyroxine in the second group. The third group received sham-operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (b-ALP). L-thyroxine administration increased the cytokines, ALP and b-ALP and decreased PTH, while there was no change in Ca and P. However, the ovariectomy of these rats did not change the levels of cytokines, Ca, P, PTH, ALP, and b-ALP. In ovariectomised rats, the cytokines, ALP and b-ALP increased but not Ca and P conversely, PTH decreased. L-thyroxine administration to ovariectomised rats did not change the levels of cytokines, Ca, P, PTH, ALP and b-ALP. In sham-operated rats there was no change in any of the parameters compared with initial values. Thyroid hormones may not be effective on bone metabolism in estrogen deficiency.
 ...
PMID:Effects of osteoporotic cytokines in ovary-intact and ovariectomised rats with induced hyperthyroidism; is skeletal responsiveness to thyroid hormone altered in estrogen deficiency? 1462 9

ATP-binding cassette (ABC) transporters [P-glycoprotein and multidrug resistance (MDR)-associated proteins (MRPs)] confer MDR to tumor cells. In this work, we investigated doxorubicin resistance in three thyroid carcinoma cell lines. The effects of sodium butyrate (NaB) on doxorubicin-induced cytotoxicity and on transcription of three MDR genes were also studied. Thyroid cell lines established from anaplastic (8505C) and two poorly differentiated follicular (FTC 238 and FTC 133) cancers were cultured for 24 or 48 h in the presence of NaB (0, 0.25, 0.5 and 1 mM) alone or combined with increased doses of doxorubicin. Cytotoxicity was assessed using the MTT test. MDR1, MRP1 and MRP2 mRNA expression was studied by RT-PCR. After a 24- or 48-h incubation, doxorubicin alone induced cytotoxicity in the three cell lines. NaB significantly (p<0.0001) increased the doxorubicin-induced cytotoxicity. MRP1 transcripts were expressed in the three non-treated cell lines. MDR1 and MRP2 mRNAs were both present in 8505C, but absent in FTC 133 or FTC 238 cell lines, respectively. Treatment with NaB for 24 or 48 h induced no change in MRP1 and MRP2 levels, but increased MDR1 expression in 8505C and FTC 238 cell lines comparably to alkaline phosphatase activity. In conclusion, MRP1 and sometimes MDR1 and MRP2 are expressed in the tested cell lines. NaB potentiates doxorubicin-induced cytotoxicity independently of the ABC transporters. The combination of doxorubicin and NaB might have clinical implications for thyroid cancer therapy.
 ...
PMID:Effect of sodium butyrate on doxorubicin resistance and expression of multidrug resistance genes in thyroid carcinoma cells. 1571 Nov 77

McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).
 ...
PMID:A case of McCune-Albright syndrome with associated multiple endocrinopathies. 1742 47

Tumor-induced osteomalacia is typically caused by benign mesenchymal tumors of vascular or skeletal origin. Overexpression of fibroblast growth factor 23 (FGF-23) by these tumors is associated with decreased resorption of phosphate in the renal tubules. This phosphate wasting leads to the characteristic findings of hypophosphatemia and hyperphosphaturia. Chronic hypophosphatemia causes abnormal mineralization of bone, increased alkaline phosphatase and, in the longer term, osteomalacia. Localization and resection of the FGF-23-secreting tumor offers the best chance of cure. We report a case of a 74-year-old woman diagnosed with numerous fractures on bone scintigraphy. Bone biopsy confirmed osteomalacia. Biochemical investigations showed hypophosphatemia, hyperphosphaturia, and increased alkaline phosphatase, suggesting the presence of an FGF-23-secreting tumor. Biochemistry also showed hyperparathyroidism and subclinical hyperthyroidism. Thyroid and parathyroid scintigraphy were performed and showed separate areas of focally increased tracer uptake in the neck. The patient underwent octreotide scintigraphy to localize an alternative site of tumor. This showed focally increased tracer uptake in the neck and in the abdomen. The patient underwent a hemithyroidectomy, parathyroidectomy, and adrenalectomy. Histopathology showed a papillary carcinoma of the thyroid, a parathyroid adenoma, and an adrenal adenoma. Postoperatively the patient showed rapid symptomatic and biochemical improvement.
 ...
PMID:Tumor-induced osteomalacia: a case of diagnostic dilemma. 1766 38

We here described a 39-year-old woman with a severe chronic mood disorder, refractory to antidepressive therapy who showed a significant improvement after a self-prescription of high doses of liothyronine (T(3)). A modified Refetoff protocol was carried out to study the role of thyroid hormones on her clinical and biochemical responses. Depression severity was assessed by the HAM-D and MADRS Depression Rating Scales. Sequencing of Thyroid Receptors (TR) alpha1 and beta1 genes was done. At the final stage of the study, plasma T3 and free T3 were >800 ng/dl (80-180) and 1409 pg/dl (230-420), respectively. No changes in the cardiovascular parameters, alkaline phosphatase isoenzymes, creatinine kinase, or ferritin were observed. However, an improvement in mood was detected by specific scores (HAM-D 24 to 8; MADRS 40 to 11). No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality. These results support the existence of a peripheral RTH manifestation as a refractory chronic depression reverted by high doses of T(3). Screening for RTH in refractory chronic depression may provide an alternative treatment for this psychiatric condition.
 ...
PMID:Refractory depression in a patient with peripheral resistance to thyroid hormone (RTH) and the effect of triiodothyronine treatment. 1790 75


<< Previous 1 2 3 4 5 6 7 Next >>