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)

The osteoblast function was evaluated in normal and diabetic children and adults by measurements of the serum concentration of the carboxy-terminal extension peptide of procollagen (PICP), total and skeletal alkaline phosphatase (ALP), and osteocalcin. Moreover, the osteoblast-stimulating growth factor, insulin-like growth factor I (IGF-I), was measured in the same samples. In normal children (n = 420; age, 5-20 yr), a marked pubertal increase of serum IGF-I (peak values at age 14-16 yr in both sexes), osteocalcin, and total and skeletal ALP (peak values earlier in girls than in boys) and a small increase in PICP were observed. All osteoblast markers and IGF-I were markedly lower in normal adults (n = 229; age, 21-69 yr) than in children. All osteoblast parameters showed a high degree of correlation (P < 0.001) with each other. In adolescents (n = 104) treated for insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was significantly increased (29%), and serum PICP remained normal. In adult IDDM (n = 125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but skeletal ALP and PICP remained normal. A similar abnormality in serum IGF-I and osteocalcin was observed in white (n = 61) and Pima Indian (n = 16) non-IDDM patients. The concentration of skeletal ALP was highly significantly correlated (r > or = 0.9) with total ALP in both normal and diabetic subjects, but the slope of the regression was significantly different, indicating the presence of other, probably intestinal, ALP in all types of diabetes. In conclusion, the osteoblast function is significantly decreased in diabetic patients, which can best be characterized as a maturation defect, since the early osteoblast marker, PICP, remained normal in all types of diabetes, whereas a later marker, skeletal ALP, is frankly abnormal only in diabetic children. The most mature osteoblast marker, osteocalcin, is decreased in all types of diabetes irrespective of age.
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PMID:Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus. 771 89

Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.
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PMID:Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation. 781 Jun 22

The cause of bone loss in patients with osteoporosis is not known, but both increased bone resorption and decreased bone formation have been reported. Theoretically, these effects may result from either increased activity of osteoclasts or decreased activity of osteoblasts, or both. In vivo, growth hormone (GH) administration leads to activation of osteoclasts and osteoblasts as evidenced by increased biochemical markers of bone resorption and bone formation. To test for disturbances in responsiveness of bone cells to exogenous hormonal stimuli in osteoporosis, we compared 15 patients with postmenopausal osteoporosis with 15 healthy age-matched postmenopausal women before and during a 3 day stimulation test with GH (0.2 IU/kg/day). Serum insulin-like growth factor I increased in both groups (p < 0.001). GH treatment increased biochemical markers of bone resorption (serum carboxyl-terminal telopeptide of type I collagen [ICTP] [p < 0.001] and, to a lesser extent, 24 h urinary hydroxyproline/creatinine) in the two groups. Similarly, biochemical markers for bone formation increased in both groups [osteocalcin (p < 0.01) and procollagen type I C-terminal propeptide, PICP (p < 0.001)]. GH treatment reduced alkaline phosphatase (ALP, p < 0.05) and its bone-specific isoenzyme (bone ALP, p < 0.01) in both groups. The maximal response, the area under the curve (AUC) of response curves for IGF-I, bone resorption markers, and bone formation markers were not different between groups. Our data do not support the hypothesis that osteoporotic patients display major disturbances in responsiveness to GH.
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PMID:Normal osteoclastic and osteoblastic responses to exogenous growth hormone in patients with postmenopausal spinal osteoporosis. 781 19

The study described here investigates the influence of a specific alimentary Zn deficiency on the concentration of growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin in the serum of force-fed rats. For this purpose 24 male Sprague-Dawley rats with an average bodyweight of 108 g were divided into 2 groups of 12 animals each. The Zn-deficient group and the control group received for 12 days a semi-synthetic casein diet with a Zn content of 1.3 and 25 ppm respectively. In order to prevent the reduced feed intake which occurs in Zn deficiency and the associated energy and protein shortage from interfering with the experimental parameters, all animals were fed 4 times daily by gastric tube. This made it possible to supply all animals with adequate-nutrients and to synchronise the feed intake exactly. After 12 days the depleted rats were in a severe state of Zn deficiency, as demonstrated by the reduction of Zn in the serum and the femur by 62% and 44% respectively and the 70% lower serum activity of alkaline phosphatase. In the Zn-deficient rats the concentration of GH in the serum was significantly increased by 78%, while IGF-1 and insulin were significantly reduced by 28% and 25% respectively. It is thought that the growth depression observed in the Zn-deficient rats in this study despite their identical feed intake is probably due to a reduced concentration of IGF-I and insulin and that the biological activity or the binding of GH to receptors is impaired in specific alimentary Zn deficiency.
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PMID:Influence of alimentary zinc deficiency on the concentration of growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin in the serum of force-fed rats. 783 22

The effects of a 16-wk strength-training program on bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in 21 men [age 61 +/- 1 (SE) yr]. Sixteen men (age 59 +/- 2 yr) served as control subjects. To investigate the possible hormonal relationships underlying the effects on BMD, serum concentrations of growth hormone, insulin-like growth factor I, and testosterone were determined before and after training. In addition, osteocalcin and skeletal alkaline phosphatase (markers of bone formation) and tartrate-resistant acid phosphatase (a marker of bone resorption) were measured before and after training to assess bone turnover. The training program resulted in a 2.8 +/- 0.6% increase in femoral neck BMD (1.004 +/- 0.037 vs. 1.031 +/- 0.037 g/cm2; P < 0.001). However, there were no significant changes in total body, anterioposterior spine, lateral spine, Ward's triangle, or greater trochanter BMD. Moreover, there were no significant changes in growth hormone, insulin-like growth factor I, testosterone, osteocalcin, or skeletal alkaline phosphatase. There were no changes in the control group. Thus, strength training can increase femoral neck BMD, and this effect does not appear to be accompanied by changes in anabolic hormones or markers of bone formation and resorption.
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PMID:Effects of strength training on bone mineral density: hormonal and bone turnover relationships. 783 86

We examined the effects of biosynthetic growth hormone (GH) on biochemical indices of bone turnover and on bone mineral density in a group of GH-deficient adults. Thirteen patients (eight males and five females) aged 24 +/- 5 years (range 16-35) were studied before and 12 and 24 months after GH treatment (0.1 IU.kg-1 day-1, 6 days a week). Serum levels of insulin-like growth factor I (IGF-I), calcitonin, parathyroid hormone, alkaline phosphatase, intact osteocalcin, fasting urinary hydroxyproline/creatinine ratio and bone mineral density (BMD), measured at the lumbar spine by dual-photon absorptiometry, were evaluated. After 12 months of treatment, IGF-I, alkaline phosphatase, osteocalcin and the fasting urinary hydroxyproline/creatinine ratio increased significantly. However, after 24 months of therapy, serum levels of osteocalcin decreased to pretreatment values while IGF-I, fasting urinary hydroxyproline/creatinine ratio and alkaline phosphatase remained elevated significantly. No changes were found in parathyroid hormone and calcitonin plasma levels or in BMD either after 12 or 24 months of treatment. These data demonstrate that GH, at the dosage that we used, activates bone turnover during 24 months of therapy in adults with panhypopituitarism, even if a downward trend for osteocalcin became apparent at 24 months. However, this activation in bone turnover was not accompanied by an increase in BMD. We can hypothesize that GH, at the relatively high dosage used, may stimulate osteoclastic activity to a greater extent than osteoblastic activity. It is probable that the dose of GH replacement therapy in adults plays a key role.
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PMID:Bone turnover and bone mineral density in young adult patients with panhypopituitarism before and after long-term growth hormone therapy. 785 9

Although mechanical forces regulate bone mass and morphology, little is known about the signals involved in that regulation. External force application increases periosteal bone formation by increasing surface activation and formation rate. In this study, the early tibial periosteal response to external loads was compared between loaded and nonloaded contralateral tibia by examining the results of blot hybridization analyses of total RNA. To study the impact of external load on gene expression, RNA blots were sequentially hybridized to cDNAs encoding the protooncogene c-fos, cytoskeletal protein beta-actin, bone matrix proteins alkaline phosphatase (ALP), osteopontin (Op), and osteocalcin (Oc), and growth factors insulin-like growth factor I (IGF-I) and transforming growth factor-beta (TGF-beta). The rapid yet transient increase in levels of c-fos mRNA seen within 2 hours after load application indirectly suggests that the initial periosteal response to mechanical loading is cell proliferation. This is also supported by the concomitant decline in levels of mRNAs encoding bone matrix proteins ALP, Op, and Oc, which are typically produced by mature osteoblasts. Another early periosteal response to mechanical load appeared to be the rapid induction of growth factor synthesis as TGF-beta and IGF-I mRNA levels were increased in the loaded limb with peak levels being observed 4 hours after loading. These data indicate that the acute periosteal response to external mechanical loading was a change in the pattern of gene expression which may signal cell proliferation. The altered pattern of gene expression observed in the present study supports previous evidence of increased periosteal cell proliferation seen both in vivo and in vitro following mechanical loading.
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PMID:Mechanical loading stimulates rapid changes in periosteal gene expression. 789 87

Responses to twice daily milk feeding, total parenteral nutrition (TPN) and fasting (saline infusion) were studied for 24 h in 1-week-old calves. Following milk intake glucose (G) and insulin (I) concentrations increased, whereas free fatty acid (FFA) and triglyceride (TG) levels and glutamate oxalacetate transaminase (GOT) and gamma-glutamyl transferase (GGT) activities decreased, while heart rate, respiration rate, rectal temperature, white blood cell number (WBC), serum iron (SFe), total protein (TP), albumin, amino acids, urea, cholesterol, sodium (Na), potassium (K), calcium (Ca), inorganic phosphorus (P(in)), insulin-like growth factor I (IGF-I), growth hormone (GH), cortisol and 3,5,3'-triiodothyronine (T3) concentrations and alkaline phosphatase (AP) activity did not change significantly. During saline infusion, Ca, G, TG, PL, I, IGF-I and T3 concentrations and AP and GGT activities decreased, while Na, FFA and urea concentrations increased. In response to TPN, G, urea, Na, tryptophane and I concentrations increased, while SFe, Ca, P(in), TG, FFA, serine, phospholipids (PL), cholesterol and T3 concentrations and AP, GOT and GGT activities decreased. Typical metabolic and endocrine changes were thus seen in response to milk intake and fasting. Changes during TPN remained within physiological limits.
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PMID:Metabolic, endocrine and haematological changes in 1-week-old calves after milk intake, in response to fasting and during total parenteral nutrition. 797 71

We present evidence that 17 beta-estradiol (17 beta-E2) regulates 1,25(OH)2D3-induced alkaline phosphatase synthesis and osteocalcin secretion by the human osteosarcoma cell line MG-63. When cells were pre-treated with 17 beta-E2 for 48 h prior to treatment with 1,25(OH)2D3 (50 nM) for another 48 h, alkaline phosphatase activity increased by 40% (P < 0.025) with 2 nM 17 beta-E2 and plateaued at levels of 20 and 200 nM 17 beta-E2. Under the same experimental conditions, osteocalcin secretion was enhanced by 37% (P < 0.005) with 2 nM E2. However, 17 beta-E2 had no effect on basal alkaline phosphatase or on osteocalcin secretion. Moreover, simultaneous addition of 17 beta-E2 and 1,25(OH)2D3 to cells did not result in any additional effect over 1,25(OH)2D3 treatment alone. Tamoxifen (10 nM) inhibited 17 beta-E2-induced activities in 1,25(OH)2D3-treated cells while not affecting control cells. Dexamethasone pretreatment (100 nM, 48 h) also stimulated alkaline phosphatase activity in MG-63 cells. Moreover, dexamethasone pretreatment followed by treatment with 17 beta-E2 and 1,25(OH)2D3 gave an additive effect for alkaline phosphatase activity. 17 alpha-Estradiol (17 alpha-E2), a less active form of estrogen, failed to modify, at low concentrations, control or 1,25(OH)2D3-induced alkaline phosphatase synthesis and osteocalcin secretion. In fact, a 100-1000-fold higher concentration of 17 alpha-E2 was necessary to reproduce the effects of 17 beta-E2 on osteocalcin secretion. The addition of insulin-like growth factor I (IGF-I) for 24 h (1-50 ng/ml) to MG-63 cells did not modify 1,25(OH)2D3-induced osteocalcin release from these cells. However, longer incubations with 50 ng/ml IGF-I did reproduce some of the effects observed with 17 beta-E2. Thus, the effects of 17 beta-E2 are probably not related to IGF-I production in MG-63 cells since under these conditions the addition of IGF-I alone should have produced a response at shorter incubation times and in the presence of lower concentrations of IGF-I. Since 17 beta-E2 pretreatment was necessary to observe any effects on 1,25(OH)2D3-induced activities, we hypothesized that 17 beta-E2 regulated 1,25(OH)2D3 receptors in MG-63 cells. When cells were treated with 100 nM 17 beta-E2 for 48 h, the binding affinity was unchanged: 37.3 +/- 1.9 versus 35.1 +/- 0.4 pM for cells whether treated or not with 17 beta-E2, respectively. In contrast, a significant increase in binding capacity (Bmax) was noted (15 +/- 3.5%; P < 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of 17 beta-estradiol on the human osteosarcoma cell line MG-63. 818 30

Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.
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PMID:Polymorphonuclear neutrophil granulocyte chemotactic hyperresponsiveness in a case of canine acromegaly. 823 7


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