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

The effect of long-term L-thyroxine (LT4) replacement therapy on bone mineral density and on biochemical markers of bone turnover were studied in children with congenital hypothyroidism (CH). Forty-four children and adolescents (mean age 8.5 +/- 3.5 years) with primary CH who began LT4 replacement therapy within the first month of life were studied. Bone mineral density (BMD) of the lumbar vertebrae and the upper femoral bone was measured by dual energy X-ray absorptiometry. Serum osteocalcin (OC) and bone alkaline phosphatase were measured as markers of bone formation and urinary deoxypyridinoline was taken as a marker of bone resorption. Bone mineral densities of CH children were not different from those in age-matched controls. The biochemical markers of bone turnover were normal except for the serum OC levels which were found to be higher than in controls and positively correlated with the free thyroid hormone levels (for FT4 r = 0.42, p = 0.02). Eight CH children demonstrated low BMD values (below -1 SDS) at -2 +/- 0.7 SDS for the lumbar spine and -1.6 +/- 0.5 SDS for the femoral site. These eight children showed lower mean weight (p < 0.05) and their dietary calcium intake tended to be less (p <0.06) than that seen in the normal BMD group. In conclusion, our results show that LT4 replacement therapy for 8 years is not detrimental to the skeletal mineralization of CH children. As in a healthy population, weight and current intake of calcium seem to be major determinants of bone density. Dietary recommendations, especially when calcium intake is below the recommended dietary allowance, may have to be reconsidered.
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PMID:Bone mineral density and metabolism in children with congenital hypothyroidism after prolonged L-thyroxine therapy. 924 Aug 77

We addressed the relationship between the thyroid status of hens and the thyroid hormone content of their eggs, as well as the influences of egg hormones on embryonic development. Methods for measuring thyroid hormones in egg yolk were verified by demonstrating consistency in the recovery of yolk thyroid hormones following a methanol/chloroform extraction and in the measurement of thyroid hormones by RIA for a range of hormone concentrations in yolk extracts. Untreated hens produced eggs with yolk thyroxine (T4) concentrations that were low relative to plasma T4, but yolk triiodothyronine (T3) concentrations comparable to those of plasma. Hens dosed twice daily with T4 (1 or 3x the daily thyroid secretion rate, TSR, of T4 per dose) had significantly higher plasma and egg yolk T4 concentrations than did control hens dosed with saline. In general, the T4 concentration of egg yolk varied with the thyroid status of the hen. When the relationship between each hen's plasma T4 and the yolk T4 concentration of her eggs was examined, hens appeared to regulate T4 deposition into yolk at "levels" characteristic of the "levels" of thyroid status produced by the different doses of T4. Embryonic pelvic cartilage, a thyroid hormone-responsive tissue, showed enhanced growth and differentiation in embryos from eggs of hens given the highest dose of T4. Specifically, alkaline phosphatase activity (a marker of differentiation) and pelvic cartilage wet and dry weights were significantly greater in embryos from high T4 eggs (hens on the 3x TSR dose) than those in controls. However, embryos from high T4 eggs did not differ in general body growth (body weight, length, and general morphology) or hatchability compared to controls. In a single T3 experiment, hens were dosed twice daily with 1 microg T3. The embryos from eggs of these hens had accelerated differentiation/maturation of pelvic cartilages (sampled at Day 12) compared to those from control eggs; body growth did not differ from that of controls.
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PMID:Maternal thyroid hormones in Japanese quail eggs and their influence on embryonic development. 924 23

In serum-containing medium, ascorbic acid induces maturation of prehypertrophic chick embryo sternal chondrocytes. Recently, cultured chondrocytes have also been reported to undergo maturation in the presence of bone morphogenetic proteins or in serum-free medium supplemented with thyroxine. In the present study, we have examined the combined effect of ascorbic acid, BMP-2, and serum-free conditions on the induction of alkaline phosphatase and type X collagen in chick sternal chondrocytes. Addition of either ascorbate or rhBMP-2 to nonconfluent cephalic sternal chondrocytes produced elevated alkaline phosphatase levels within 24-72 h, and simultaneous exposure to both ascorbate and BMP yielded enzyme levels at least threefold those of either inducer alone. The effects of ascorbate and BMP were markedly potentiated by culture in serum-free medium, and alkaline phosphatase levels of preconfluent serum-free cultures treated for 48 h with BMP+ascorbate were equivalent to those reached in serum-containing medium only after confluence. While ascorbate addition was required for maximal alkaline phosphatase activity, it did not induce a rapid increase in type X collagen mRNA. In contrast, BMP added to serum-free medium induced a three- to fourfold increase in type X collagen mRNA within 24 h even in the presence of cyclohexamide, indicating that new protein synthesis was not required. Addition of thyroid hormone to serum-free medium was required for maximal ascorbate effects but not for BMP stimulation. Neither ascorbate nor BMP induced alkaline phosphatase activity in caudal sternal chondrocytes, which do not undergo hypertrophy during embryonic development. These results indicate that ascorbate+BMP in serum-free culture induces rapid chondrocyte maturation of prehypertrophic chondrocytes. The mechanisms for ascorbate and BMP action appear to be distinct, while BMP and thyroid hormone may share a similar mechanism for induction.
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PMID:Rapid chondrocyte maturation by serum-free culture with BMP-2 and ascorbic acid. 925 95

The mechanism of action of thyroid hormones on bone is poorly understood. Thyroid hormones may act on bone cells either indirectly by increasing secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), or directly by influencing target genes via specific nuclear receptors. The presence of thyroid hormone receptors (TRs) has been demonstrated in human and rodent osteoblast-like cells and cell lines and recently in osteoclasts derived from an osteoclastoma in vitro. However, their presence in human bone in situ has not been reported. We have used specific polyclonal antibodies to TR-alpha 1, -alpha 2, and -beta 1 to investigate the expression of these receptors in sections of human osteophytes and heterotopic bone. Osteoblasts and osteoclasts were identified by alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), respectively, whereas chondrocytes were identified morphologically. At sites of endochondral and intramembranous bone formation, TR-beta 1 and the splice variant -alpha 2 were widely expressed by proliferating, mature, and hypertrophic chondrocytes and also in cells within the fibrous tissue and at the bone forming surfaces, respectively. They were also detected in osteoblasts, osteoclasts, and a few osteocytes at sites of bone remodeling. In contrast, TR-alpha 1 was the least expressed and was present mainly in osteoblasts at remodeling sites and in a few mature and undifferentiated chondrocytes. Our results show, for the first time, the presence and distribution of TRs in human bone in situ and suggest that the skeletal actions of thyroid hormones may be mediated via these receptors. Further studies are required to define the role of the individual receptor isoforms in bone metabolism.
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PMID:The expression of thyroid hormone receptors in human bone. 926 88

Hyperthyroidism increases bone turnover and induces bone loss. This study examines the effect of thyroid hormone excess on two biochemical markers of bone turnover (hydroxyproline and bone alkaline phosphatase) as well as on bone mineral content (BMC) and bone mineral density (BMD). The possible protective role of dimethyl-APD (olpadronate, OLP), on both suppression of bone turnover and bone mineral loss in ovariectomized (ovx) rats, was also studied. Female Sprague-Dawley rats, were assigned to five groups of eight rats each: sham, ovx, ovx OLP treated (0.3 mg/kg per week), ovx T4 treated (250 micrograms/kg per day), and ovx T4-OLP rats. Rats were killed after 5 weeks of treatment. At the end of the study, blood samples were analyzed for serum calcium, phosphorus, T4, total and bone alkaline phosphatase (ALP and b-ALP), and urinary samples for hydroxyproline/creatinine ratio (HOProl/creat). Moreover, total BMC, BMD, and scanned area were determined by DXA. Ovx T4-OLP-treated rats presented higher values of b-ALP than ovx T4-treated, ovx, and sham rats (p < 0.05). Ovx increased HOProl/creat excretion compared with sham (p < 0.05), but it was similar compared with ovx T4-treated rats. OLP treatment reduced HOProl/creat excretion in both ovx T4-treated (p < 0.05) and ovx rats (p < 0.05). The final BMC in ovx was lower than in the sham group, but the difference was not statistically significant (p < 0.08). The lowest BMC was observed in ovx T4 rats (p < 0.05). When final BMC was expressed per body weight (BMC/W), ovx rats presented a significantly lower BMC/W than sham rats (p < 0.05). Ovx OLP rats had BMC/W levels higher than ovx (p < 0.005), ovx T4 (p < 0.01), and ovx T4-OLP rats (p < 0.01). The ovx group had a final BMD lower than sham animals (p < 0.05), but not significantly different than the ovx T4 rats. BMC and BMD of OLP ovx rats, whether they received T4 or not, was similar to the sham group. The highest final BMD was observed in the ovx T4-OLP group. In summary, the prevention of an increase in HOProl excretion accompanied by the fact that final BMD and BMC in OLP-treated animals were comparable to sham control rats may reflect that OLP administration could inhibit bone resorption in both T4-treated or -untreated rats. Although further studies are necessary, these findings may have clinical relevance in estrogen-depleted patients to whom medical management other than the reduction of T4 administration would be desirable.
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PMID:The effect of olpadronate in ovariectomized thyroxine-treated rats. 931 36

We evaluated the effects of the thyroid hormone on bone and mineral metabolism in rats using biochemical markers [pyridinoline (Pyr), deoxypyridinoline (Dpyr), Osteocalcin (OC), alkaline phosphatase (Alp)] and the measuring of bone mineral density (BMD). First, the rats were divided into three groups: 1) control group 2) The fifty micrograms group (T3-50) [It was given 50 micrograms/kg ip/day of triiod-l-thyronine (T3) for 2 weeks.] 3)The hundred micrograms group (T3-100) [It was given 100 micrograms/kg ip/day of T3 for 2 weeks.] Next, the rats were divided into two groups: 1)control group and 2)T3 group. The latter was given 100 micrograms/kg of T3 ip/day for 4 weeks. In experiment 1, Pyr and Dpyr levels in the T3 groups were significantly higher or well tended to be higher than those in the control group. OC levels in the T3 groups were significantly higher than in the control group until day 7. The Z-score of Pyr and Dpyr in T3-100 were two to thirteen times higher than those of OC and Alp. In experiment 2, Pyr and Dpyr levels in the T3 group were significantly higher or well tended to be higher than those in the control group. OC levels in the T3 group were significantly higher than those in the control group only on day 3. In the present study, the administering of T3 100 micrograms decreased both cortical (tibia) and trabecular (lumbar spine) BMDs in the rats. Bone resorption continued to increase after increased bone formation was reduced by T3 administration. Furthermore, bone resorption exceeded bone formation throughout T3 administration.
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PMID:Effect of thyroid hormone on bone and mineral metabolism in rat: evaluation by biochemical markers. 937 4

Endochondral ossification in growth plates proceeds through several consecutive steps of late cartilage differentiation leading to chondrocyte hypertrophy, vascular invasion, and, eventually, to replacement of the tissue by bone. It is well established that the subchondral vascular system is pivotal in the regulation of this process. Cells of subchondral blood vessels act as a source of vascular invasion and, in addition, release factors influencing growth and differentiation of chondrocytes in the avascular growth plate. To elucidate the paracrine contribution of endothelial cells we studied the hypertrophic development of resting chondrocytes from the caudal third of chick embryo sterna in co-culture with endothelial cells. The design of the experiments prevented cell-to-cell contact but allowed paracrine communication between endothelial cells and chondrocytes. Under these conditions, chondrocytes rapidly became hypertrophied in vitro and expressed the stage-specific markers collagen X and alkaline phosphatase. This development also required signaling by thyroid hormone in synergy. Conditioned media could replace the endothelial cells, indicating that diffusible factors mediated this process. By contrast, smooth muscle cells, fibroblasts, or hypertrophic chondrocytes did not secrete this activity, suggesting that the factors were specific for endothelial cells. We conclude that endochondral ossification is under the control of a mutual communication between chondrocytes and endothelial cells. A finely tuned balance between chondrocyte-derived signals repressing cartilage maturation and endothelial signals promoting late differentiation of chondrocytes is essential for normal endochondral ossification during development, growth, and repair of bone. A dysregulation of this balance in permanent joint cartilage also may be responsible for the initiation of pathological cartilage degeneration in joint diseases.
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PMID:Role of the subchondral vascular system in endochondral ossification: endothelial cells specifically derepress late differentiation in resting chondrocytes in vitro. 947 58

Although a substantial coronary angiogenesis occurs after thyroid hormone treatment, its regulation and relationship to cardiac hypertrophy are not understood. This study was designed to determine (1) the onset of capillary proliferation, (2) the sites of capillary proliferation, and (3) whether basic fibroblast growth factor (bFGF) upregulation occurs in response to thyroxine administration. Male Sprague-Dawley rats were injected daily with L-thyroxine (T4, 0.2 mg/kg s.c.). Bromodeoxyuridine labeling of capillary endothelial cells increased during the first 24 hours of treatment and peaked after 2 days of treatment. Northern blot analysis revealed a slight increase in bFGF mRNA during this period, followed by a doubling of expression by 48 hours, at which time bFGF protein was also increased. In situ hybridization, used to localize bFGF mRNA, showed an increase in transcripts within 24 hours after T4. This enhancement was uniform in the epimyocardium and endomyocardium. Histochemical analysis (double staining for alkaline phosphatase and dipeptidyl peptidase) of frozen sections, used to discriminate capillary profiles as arteriolar and venular, respectively, showed that growth occurred in the latter, since the percentage of capillary profiles positive for dipeptidyl peptidase was higher than the control value after 4 days of T4 administration. These data indicate that in the thyroxine model of cardiac hypertrophy (1) capillary DNA synthesis occurs after a single injection of thyroxine, (2) capillary growth coincides with an upregulation in bFGF mRNA and increase in bFGF protein, and (3) proliferation occurs in the venular capillaries.
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PMID:Early coronary angiogenesis in response to thyroxine: growth characteristics and upregulation of basic fibroblast growth factor. 952 63

In an ovariectomized rat model of osteoporosis, the effects of cold stress on intestinal Ca2+ transference and rate of bone turnover were evaluated. In the ovariectomized rats, a significant reduction in intestinal transference of Ca2+ was associated with decreased activities of intestinal mucosal enzymes, alkaline phosphatase (AP), and calcium ATPase (Ca2+-ATPase) in all the different segments of small intestine in a descending gradient. The development of a high rate of bone turnover and osteoporosis in these animals was confirmed by significant alteration in plasma AP activity and calcium (Ca) level, urinary excretion of Ca and phosphate, and Ca : creatinine ratio. Cold stress in this model, apart from its unique influence in elevating plasma corticosterone and thyroid hormone level, enhanced all the above referred parameters studied in connection with intestinal transference of Ca2+, bone turnover rate, and osteoporosis. The results of this study emphasize that cold stress may have a positive influence on bone loss for an early development of hypogonadal osteoporosis in rats.
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PMID:Cold stress facilitates calcium mobilization from bone in an ovariectomized rat model of osteoporosis. 953 89

Thyroid hormones (T3 and T4) regulate bone development, growth, and turnover. Studies have suggested that different skeletal sites respond differently to thyroid hormones. Therefore, we examined the in vitro T3 responsiveness of cells committed to the osteoblast lineage as a function of skeletal location. Bone marrow cells derived from female rat femurs and vertebrae were cultured using conditions that induce osteogenic differentiation. Cells from both sites formed mineralized bone nodules in primary and secondary culture. In femoral cultures, collagen type I (coll I) and osteocalcin (OC) messenger RNA (mRNA) levels increased from the earliest time point examined (day 3) to a maximum on day 12 and thereafter declined to undetectable levels. T3 increased both OC and coll I mRNA, resulting in a continuous expression throughout the culture period. Insulin-like growth factor I (IGF-I) gene expression was detected at very low levels by Northern analysis of femoral total RNA, and T3 only marginally enhanced IGF-I mRNA levels. In vertebral cultures, OC and coll I mRNA levels also increased with time in culture, but remained expressed throughout the culture period. OC and coll I mRNA levels were not markedly altered in response to T3. In contrast to femoral cells, IGF-I gene expression was easily visualized in Northern blots from untreated vertebral cultures and was markedly increased by the addition of T3. The continuous presence of T3 (10(-7) M) in the medium for 18 days caused a marked decrease in the number of alkaline phosphatase-positive colonies formed in femoral secondary cultures, but only a slight decrease in the number in vertebral cultures. In addition, short term (6 days) exposure to T3 (10(-7) M) at the beginning of the culture period decreased alkaline phosphatase activity in femoral cultures, but not in vertebral cultures. These findings indicate that there are skeletal site-dependent differences in the in vitro responses of cells of the osteoblastic lineage to thyroid hormone.
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PMID:Thyroid hormone excess increases insulin-like growth factor I transcripts in bone marrow cell cultures: divergent effects on vertebral and femoral cell cultures. 956 68


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