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)

Serum bone Gla protein (BGP) and bone alkaline phosphatase (B-AP), markers of bone formation, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), marker of bone resorption, and aminoterminal propeptide of type III procollagen (PIIINP) levels, index of collagen synthesis, were determined in 8 adults (mean age +/- SE: 29.6 +/- 1.2 yr) with childhood onset GHD before and after 3 and 6 months of recombinant GH treatment (0.5 IU/kg/week). Before treatment, mean BGP (3.8 +/- .5 ng/ml) and B-AP (44.9 +/- 6.9 IU/L) were significantly (P < 0.001 and p < 0.05, respectively) lower than those recorded in normals (5.4 +/- 0.1 ng/ml and 61.8 +/- 1.9 IU/L, respectively), while serum ICTP and PIIINP levels were similar to those found in controls (ICTP: 4.7 +/- 0.8 vs 4.1 +/- 0.3 ng/ml; PIIINP: 3.7 +/- 0.6 vs 3.2 +/- 0.2 ng/ml). BGP and ICTP levels significantly (p < 0.005) increased after 3 (28.4 +/- 5.3 ng/ml and 17.5 +/- 2.8 ng/ml, respectively) and 6 months (25.1 +/- 5.0 ng/ml and 15.0 +/- 1.9 ng/ml, respectively) of recombinant GH treatment. B-AP levels significantly (p < 0.01) increased during the treatment (basal: 44.9 +/- 6.9 IU/L, 3rd month: 173.6 +/- 40 IU/L, 6th month: 194.4 +/- 40 IU/L), while non B-AP levels remained similar to those recorded in basal condition. Serum PIIINP levels significantly (p < 0.0001) rose up after 3 (12.5 +/- 1.4 ng/ml) and 6 months (10.2 +/- 0.8 ng/ml). Serum BGP and ICTP levels were directly (r = 0.85, p < 0.001; r = 0.53, p < 0.01) correlated with serum IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Growth hormone treatment in adults with GH deficiency: effects on new biochemical markers of bone and collagen turnover. 814 66

To evaluate the osteoblastic function in patients with multiple pituitary hormone deficiencies (M-PHD) and with isolated growth hormone deficiency (I-GHD), bone cells were cultured and the effects of 10(-8) M 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH)2D3 treatment increased alkaline phosphatase activity and osteocalcin release but inhibited [3H]thymidine incorporation in all cell cultures from patients as well as from controls. In addition, 1,25(OH)2D3 increased the release of both total and active transforming growth factor-beta (TGF-beta) in bone cells from controls by, respectively, 4.9- and 3.2-fold and in bone cells from I-GHD by 5.1- and 1.5-fold, respectively. However, in bone cells from M-PHD, the stimulation of total TGF-beta release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-beta release was not stimulated at all. One year of supplementation with human growth hormone did not improve this deficient TGF-beta release in bone cells from M-PHD. We conclude that cultured bone cells from I-GHD and M-PHD show a normal response to 1,25(OH)2D3 regarding cell proliferation and osteoblastic differentiation, which implicates a normal 1,25(OH)2D3-receptor function. In cells from controls and I-GHD, 1,25(OH)2D3 enhanced both total and active TGF-beta release. However, bone cells from M-PHD showed a deficient TGF-beta response to 1,25(OH)2D3. These results suggest that the regulation of TGF-beta production is a major paracrine factor involved in hypopituitarism.
 ...
PMID:1,25-dihydroxyvitamin D3-mediated transforming growth factor-beta release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies. 885 47

Serum bone-Gla protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels were evaluated in 18 adults with acquired GH deficiency (GHD, 14 males and 4 females, age range: 25-59 yr) before, at 3, 6, 9 and 12 months of rec-GH treatment (0.125 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 months) and 6 months after the withdrawal of therapy. Total body bone mineral density (BMD, g/cm2) was measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) before, at 12 months of GH treatment and 6 months after its withdrawal. Before treatment, BGP (mean+/-SE: 5.1+/-0.4 ng/ml), B-AP (59.4+/-6.5 IU/l), ICTP (3.1+/-0.3 ng/ml) levels of patients were similar to in healthy controls (BGP: 5.4+/-0.1 ng/ml; B-AP: 58.2+/-2.0 IU/l; ICTP: 4.1+/-0.3 ng/ml). GH treatment caused a significant increase of BGP, B-AP, ICTP levels, the maximal stimulation of bone resorption, occurring after 3 months of GH treatment, while the maximal effect on bone formation being evident later (at 6th month). A slight decline in BGP, B-AP, T-AP and ICTP levels occurred at 9-12 months of therapy, although the values remained significantly higher than in basal conditions and with respect to healthy controls. Before treatment, mean total body BMD of patients (1.110+/-0.027 g/cm2, range: 0.944-1.350 g/cm2) was not significantly different (z-score: +0.47+/-0.31, NS) from that observed in healthy controls (1.065+/-0.008 g/cm2, range: 1.008-1.121 g/cm2). GH therapy was associated with a significant reduction of mean total body BMD values (6th month: -1.8+/-0.5%, p<0.01; 12th month: -2.1+/-1.0%, p<0.05 vs baseline), particularly evident in the first six months of treatment. Six months after the withdrawal of GH therapy, BGP (5.9+/-0.5 ng/ml), B-AP (57.3+/-7.0 IU/l) and ICTP (3.2+/-0.1 ng/ml) levels returned similar to those recorded before treatment, while total BMD increased (+1.5+/-0.7, p<0.05), remaining however slightly lower than in basal conditions (-0.6+/-1.2, NS). In conclusion, our study shows that: a) acquired GHD in adulthood is associated with both normal bone formation/resorption indexes and normal total body BMD; b) GH therapy causes a significant rise of bone formation/resorption markers (earlier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the first 6 months of treatment; d) the effects of GH therapy on bone turnover are transient, being completely reverted six months after the withdrawal of GH therapy; e) the increase of total body BMD (up to baseline values) after GH withdrawal might be explained as consequence of persisting effects of previous GH stimulation on bone remodeling.
 ...
PMID:Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency. 1138 8