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)

Bone formation was studied after intramuscular implantation of demineralized bone matrix. Ash weight determinations were used to verify the bone-forming ability of implants, and confirmed that no bone was formed when nonactive implants (stripped of their bone-forming ability) were used. A solution hybridization/RNase protection assay was used for the detection of specific mRNA transcripts in the implants and surrounding tissue. Analysis of insulin-like growth factor I (IGF-I) mRNA showed a transient increase peaking on day 3 following implantation. Radioimmunoassay (RIA) for IGF-I-like immunoreactivity indicated a corresponding increase of IGF-I peptide in extracts from the implants at that time point. IGF-II mRNA and alkaline phosphatase mRNA reached highest levels around day 11 following implantation. Bone formation in old rats, 50 weeks of age, was associated with lower IGF-I mRNA levels 3 days after implantation compared with young animals. IGF-II mRNA levels were also affected and tended to be higher 12 days after implantation compared with young animals. These results indicate that IGFs could be paracrine or autocrine factors in the bone-forming process. During this process, IGF-I mRNA is expressed at an early stage, in correlation with the recruitment and proliferation of surrounding mesenchymal cells, whereas IGF-II mRNA is activated significantly later, correlating to the beginning of the actual calcifying process during endochondral bone formation.
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PMID:Expression of insulin-like growth factors during bone induction in rat. 824 73

Serum bone Gla protein, a sensitive and specific marker of bone turnover, was measured in 35 acromegalic patients (14 untreated, 8 clinically active, and 13 cured) and 21 controls. We also examined 10 acromegalic patients before and after transsphenoidal surgery. Untreated and clinically active acromegalic patients had significantly higher serum bone Gla protein concentrations than the control subjects. Other nonspecific biochemical markers of bone metabolism, such as urinary hydroxyproline and urinary calcium, were also present in significantly greater amounts in active acromegalic patients. After treatment, a significant decrease in levels was observed, with return to control levels. In acromegalic patients, positive correlations were found among serum bone Gla protein and serum growth hormone and serum insulin-like growth factor I levels, as well as among levels of insulin-like growth factor I and serum phosphorus, serum alkaline phosphatase, and urinary hydroxyproline. These results suggest that serum bone Gla protein is a sensitive marker of the action of growth hormone in bone metabolism in acromegaly, a role that is probably mediated by insulin-like growth factor I.
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PMID:Serum bone Gla protein as a marker of bone turnover in acromegaly. 836 87

Following injury to bone marrow there is a phase of osteogenesis in which bone trabeculae replace the initial blood clot and fill the marrow cavity. The newly formed bone is subsequently fully resorbed by osteoclasts and normal bone marrow is restored. In this study we correlated the morphologic events with the pattern of gene expression that defines this sequence. Following marrow ablation, the trabecular bone volume in the affected section of the marrow cavity increased from control to 27% at day 6, declined to 18% at day 8, and eventually returned to control levels at day 14. Osteoblast number increased up to day 6 and declined substantially by day 8, but the number of osteoclasts peaked between days 8 and 10. Histologic analysis of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activity correlated with the observed cellular changes. Northern blot analysis of the levels of AP, osteocalcin (OC), and osteopontin (OP) mRNA shows a specific pattern of regulated gene expression, with AP mRNA maximal at day 6, OC mRNA very low until days 6-8, and OP mRNA expressed at very high levels throughout. In addition, procollagen alpha 1(I) and alpha 1(III) mRNAs show a regulated pattern of expression, with procollagen alpha 1(I) maximally expressed between days 4 and 10 and procollagen alpha 1(III) expressed at lower levels between days 4 and 6. The mRNA encoding insulin-like growth factor I (IGF-I) was found to be highly expressed between days 5 and 12; however, transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 3 mRNA were only weakly expressed between days 4 and 10. These data demonstrate a temporal pattern of gene expression consistent with the observed morphologic profile, identify changes in growth factor mRNA that may be related to this repair process, and suggest that this is a suitable model for studying in vivo a synchronized sequence of bone formation and resorption at a well-defined anatomic site.
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PMID:Pattern of gene expression following rat tibial marrow ablation. 845 91

Forty-eight Angus x Hereford steers (initial BW = 336 +/- 8.3 kg) were used in a 56-d study to evaluate growth and endocrine responses to continuous or discontinuous grazing of high-endophyte-infected Kentucky-31 (K; > 57% infestation rate) or low-endophyte-infected Johnstone tall fescue (J; < 1% infestation rate) and implantation with 0 or 24 mg/steer of estradiol-17 beta (E2; Compudose). Steers were allotted by weight to eight 3-ha paddocks (four paddocks of each fescue variety) with six steers per paddock. Two paddocks of each variety were grazed continuously (KK and JJ), whereas steers on the remaining four paddocks were rotated every 14 d from K to J (KJ) or from J to K (JK). Three steers in each paddock were implanted with E2 on d 0. The study extended from May 25, 1988 to July 20, 1988 with steers exposed to potential heat-stress conditions for 52 d of the 56-d study. Body weights were obtained on d 0, 28, and 56, and blood samples were taken on d 28 and 56. Overall ADG, serum prolactin, and serum alkaline phosphatase activity were greater (P < .05) in JJ than in KK steers. Rotation from K to J did not increase overall ADG, prolactin, insulin-like growth factor I (IGF-I), or alkaline phosphatase activity compared with the continuously grazed KK, whereas JK steers had lower (P < .10) ADG, prolactin, and alkaline phosphatase activity than JJ steers. Estradiol-17 beta increased (P < .10) IGF-I in JJ, KJ, and JK steers but not in KK steers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth and endocrine responses of cattle to implantation of estradiol-17 beta during continuous or discontinuous grazing of high- and low-endophyte-infected tall fescue. 846 63

Osteogenic protein-1 (OP-1) is a member of the bone morphogenetic protein family and has been shown to induce new bone formation in vivo. In the present study, we determined whether the expression of the IGF system, a significant growth factor system in bone, was altered by OP-1 in primary cultures of fetal rat calvarial cells. Levels of messenger RNA (mRNA) encoding insulin-like growth factor I (IGF-I), IGF-II, IGF-I receptor, and IGF-binding proteins (IGFBP-1 to -6) were determined after OP-1 treatment. The level of total IGF-I mRNA was elevated in an OP-1 concentration (0-1000 ng/ml)-dependent manner, with maximal stimulation of IGF-I mRNA of 2- to 3-fold apparent 24 h after treatment. The increase in the IGF-I mRNA level involved a preferential stimulation of transcripts initiated at start site 2 in the exon 1 promoter. The level of IGF-II mRNA also increased by approximately 2-fold in OP-1 treated cells in a concentration-dependent manner. The level of IGF-I receptor mRNA was not altered by treatment. Whereas IGFBP-1 mRNA was not detected in these cells, IGFBP-2 mRNA was expressed, but the expression was not changed after treatment for 48 h in the concentration range (0-1000 ng/ml) tested. The IGFBP-3 mRNA level was increased slightly 48 h after OP-1 treatment in a concentration-dependent manner. The IGFBP-4, -5, and -6 mRNA levels decreased dramatically in an OP-1 concentration-dependent manner. In addition, coincubation of antisense oligonucleotides corresponding to IGF-I or -II mRNA sequence with OP-1 reduced the OP-1 induced elevation in alkaline phosphatase activity. The present results suggest that the differentiation of rat osteoblastic cells in response to OP-1 is mediated in part by increased IGF-I -II gene expression and alterations in the gene expression of different IGFBPs.
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PMID:Osteogenic protein-1-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells. 861 32

The effects of GH substitution on skeletal mass, bone turnover, and calcium metabolism were investigated in 29 patients with GH deficiency who were randomized to sc injections with GH (2 IU/m2 day) or placebo for 12 months. During GH treatment, serum insulin-like growth factor I increased 263 +/- 98% (P < 0.001). Serum osteocalcin, bone a alkaline phosphatase, and procollagen type I C-terminal propeptide increased by 376 +/- 78% (P < 0.005), 128 +/- 17% (P < 0.005), and 100 +/- 17% (P < 0.005), respectively. Serum type I collagen telopeptide and urinary levels of pyridinoline, deoxypyridinoline, and hydroxyproline rose by 158 +/- 39% (P < 0.005), 170 +/- 48% (P < 0.005), 156 +/- 78% (P < 0.005), and 161 +/- 50% (P < 0.005), respectively. Serum ionized calcium rose by 1.7 +/- 0.6% (P < 0.05), whereas serum PTH decreased insignificantly. Vitamin D metabolites remained unaltered. Urinary calcium/creatinine increased and phosphate/creatinine decreased transiently, returning to baseline values at 9 months. When measured by dual energy x-ray absorptiometry, whole body bone mineral density (BMD) and (BMD) of the radius decreased 2.4 +/- 0.6% (P < 0.05) and 3.5 +/- 1.0% (P < 0.005), respectively, whereas no significant changes were observed in BMD of the femur or spine. Our results indicate that long term GH treatment activates bone remodeling in patients with GH deficiency. The observed slight decrease in BMD may be explained by expansion of the remodeling space and reduced mean age of bone tissue. IT remains unclear whether long term treatment with GH will lead to an increase in bone mass and improved skeletal biomechanical competence.
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PMID:Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. 878 96

Responses to i.v. injected E. coli endotoxin (E), followed by saline infusion, as compared with saline infusion alone, were studied for 24 h in 1-week-old calves. After administration of E, respiratory rate (RR), heart rate (HR), rectal temperature (RT), serum iron, insulin, (I), cortisol and tumor necrosis factor-alpha, transiently, and urea, continuously, increased. Isoleucine and leucine became elevated at 24 h, whereas white-blood-cell number, free fatty acids (FFA) and triglycerides (TG) increased after an initial fall. After administration of E, packed-cell volume, erythrocyte number, haemoglobin, glucose (G), cholesterol, phospholipids (PL), lysine, arginine, proline, citrulline, calcium (Ca), inorganic phosphorus, insulin-like growth factor I (IGF-I) and 3,5,3'-triiodothyronine (T3) concentrations and alkaline phosphatase (AP) and gamma-glutamyl transferase (gamma GT) activities increased significantly while growth hormone decreased non-significantly. When saline was infused alone, G, TG, PL, Ca, AP, gamma GT, I, IGF-I and T3 decreased, while FFA, urea and sodium increased, but, changes of G, urea, AP, IGF-I and T3 were less marked than after injection of E. Potassium, total protein and albumin concentrations, and glutamyl dehydrogenase and glutamate oxalacetate transaminase activities were not significantly affected by either treatment. In conclusion, metabolic and endocrine changes during saline infusion alone were typical for food withdrawal. Changes of variables after administration of E were transient, biphasic or sustained, thus expressing complex interactions between metabolic parameters, endocrine factors and cytokines.
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PMID:Metabolic, endocrine and haematological responses to intravenous E. coli endotoxin administration in 1-week-old calves. 883 Dec 69

Hexarelin (HEXA; 500 micrograms/kg/die, s.c.) was administered for 16 weeks to six old beagle dogs. The treatment consisted of three on-drug periods spaced by two off-drug periods. During each on period, the growth hormone (GH) peak response to HEXA initially increased and then dropped to pretreatment values. Each time, a wash-out interval restored the same pattern of GH responsiveness. HEXA significantly augmented the indices of spontaneous pulsatility of GH, but plasma insulin-like growth factor I levels did not change during treatment. HEXA apparently reduced bone resorption since it significantly decreased the urinary concentration of lysylpyridinoline, a bone matrix component. Bone formation apparently was not affected since unchanged levels of alkaline phosphatase were recorded. In three of six old dogs, HEXA induced an improvement of some morphological and biochemical muscular indices, evaluated in muscle specimens that, instead, remained unchanged in a group of young untreated controls. These findings indicate that HEXA effectively releases GH and primes the pituitary of old dogs, and strengthen the view that in aging, GH secretion may be restored by pharmacological means. It would also appear that HEXA-induced GH release improves some indices of body composition in old dogs.
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PMID:Sixteen weeks of hexarelin therapy in aged dogs: effects on the somatotropic axis, muscle morphology, and bone metabolism. 891 94

The effects of treatment with estrogens and antiandrogens in male to female (M-->F) transsexuals and androgens in female to male (F-->M) transsexuals on their respective bone metabolism, bone mineral density (BMD), serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels were investigated. BMD and variables of bone turnover in serum were measured at baseline and after 3 months (except for BMD) and 1 yr of treatment in 56 M-->F and 35 F-->M transsexuals. Serum IGF-I, IGFBP-3, and propeptide of type I procollagen (P1CP) were measured at baseline and after 1 yr of treatment in 10 M-->F and 10 F-->M transsexuals. In M-->F, BMD increased significantly. Bone turnover decreased, as shown by a significant decline in levels of osteocalcin, alkaline phosphatase, P1CP, and fasting urinary calcium/creatinine and hydroxyproline/creatinine ratios. Serum IGF-I levels decreased significantly without significant changes in IGFBP-3 levels. In F-->M, BMD did not change. Bone formation increased, as suggested by an increase in alkaline phosphatase and a borderline increase in P1CP values. IGF-I levels increased significantly, whereas no significant changes were seen in IGFBP-3 levels. We conclude that in males, estrogens (in combination with antiandrogens) decrease bone turnover, with a subsequent increase in BMD and a decrease in serum IGF-I. In females, testosterone administration increases bone formation, but this is not reflected in an increased BMD, whereas serum IGF-I increases.
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PMID:The effect of one-year cross-sex hormonal treatment on bone metabolism and serum insulin-like growth factor-1 in transsexuals. 896 56

Thirty-six patients with adult-onset GH deficiency (GHD) were examined before and after 9 months of treatment with recombinant GH. The study was conducted as a double blind, placebo-controlled, 21-month trial with a cross-over design, with each treatment period lasting for 9 months. The same dose, adjusted for body surface area, was given to men (n = 21) and women (n = 15), and the effects on body composition and biochemical parameters were evaluated with respect to gender. The extent of GHD, assessed before therapy from basal GH secretion and GH release in response to provocative tests, did not differ between the two groups. The men, however, had higher serum insulin-like growth factor I concentrations than the women (mean +/- SD, 126 +/- 71 vs. 61 +/- 32 micrograms/L; P = 0.0003), less body fat, and greater lean body mass. Upon treatment, insulin-like growth factor I concentrations increased more in men than in women (by 305 +/- 136 and 198 +/- 96 micrograms/L, respectively; P = 0.02). The men lost more body fat than the women (7.4 +/- 4.1% vs. 3.3 +/- 3.8%; P = 0.002), whereas the difference in gain in lean body mass failed to reach statistical significance. Serum levels of total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and plasminogen activator inhibitor-1 decreased in the male group (P = 0.003, P = 0.03, P = 0.0009, and P = 0.01, respectively), but not in the females. Serum markers of bone formation, namely osteocalcin, procollagen type I, bone-specific alkaline phosphatase, and a marker of bone resorption, telopeptide of collagen type I, increased more markedly in men than in women. Lipoprotein(a) increased to a similar extent in the male and female groups. The data demonstrate that men and women with GHD display marked differences in their responsiveness to GH replacement therapy. These differences should be taken into consideration when optimizing the treatment of GHD patients.
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PMID:Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. 932 96


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