Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine which clinical, anthropometric, dietary, and biochemical variables are independent predictors of total and regional bone mineral density (BMD) in normal postmenopausal women, a cross-sectional study of 140 normal postmenopausal women has been carried out. Subjects were white, aged 45-71 yr (mean 58 yr), and had no history of disorders or medication use likely to influence bone or calcium metabolism. Multiple regression analysis was used to derive models for total and regional BMD in terms of the other variables measured. The analysis indicated that total body BMD was positively related to fat mass (P less than 0.0001), serum estrone (P = 0.0095) and age at menopause (P = 0.0165), and negatively related to age (P less than 0.0001), 24-h urine calcium (P = 0.0002), sex hormone-binding globulin (P = 0.0003), and serum alkaline phosphatase activity (P = 0.0029) (R2 = 0.61). Similar relationships were found in the subregions of the total body scans and in the lumbar spine and proximal femur, with insulin-like growth factor-1, parity, and age at menarche also being related to BMD at at least two of these sites. Lean body mass was not an independent correlate of BMD at any site once fat mass was taken into account. Muscle strength, physical activity, alcohol intake, and dietary intakes of calcium, sodium and protein did not emerge as significant predictors of BMD in this homogeneous group of postmenopausal women. We conclude that total body fat is the most significant predictor of BMD throughout the skeleton and this relationship is not explicable in terms of either estrone production in fat tissue or the dependence of skeletal load-bearing on fat mass. The mechanism underlying this relationship is an important question to be addressed in bone biology.
...
PMID:Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat mass. 161 30

The hormonal and biochemical effects of danazol (600 mg a day) and high-dose medroxyprogesterone acetate (MPA; 100 mg a day) were studied in a placebo-controlled, 6-month trial. Serum gonadotrophins and prolactin levels did not change during danazol and MPA treatments, whereas oestradiol and progesterone levels decreased significantly in relation to placebo without any difference between danazol and MPA. Both drugs significantly suppressed the sex hormone-binding globulin level (SHBG), and consequently, the free-androgen index (serum total testosterone nmol/l per SHBG nmol/l x 100) as compared with placebo, the effect of danazol being significantly stronger than that of MPA. Danazol, but not MPA, significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and haemoglobin levels, and also thrombocyte counts, whereas MPA, but not danazol, increased the serum concentration of albumin in relation to placebo. Serum total bilirubin, conjugated bilirubin, gamma-glutamyl transferase, creatinine, alkaline phosphatase, sodium and potassium levels and leucocyte counts remained unchanged during both treatments. Danazol and high-dose MPA did not differ from each other in their ovarian and anterior pituitary effects, while the increase in androgenic activity induced by danazol was greater than that achieved with MPA. Danazol also had more biochemical effects than MPA. It interfered with the functions of the liver and the production of thrombocytes and haemoglobin, whereas MPA affected only albumin synthesis/release.
...
PMID:Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate. 214 9

We investigated the influence of L-thyroxine (L-T4) treatment over 3 weeks on biochemical markers of bone turnover in 12 healthy young men (age 25.6 +/- 1.4 years, BMI: 22.6 +/- 2.5 kg/m2). Serum parameters indicating bone formation [bone Gla protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and bone-specific alkaline phosphatase (BAP)] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and the urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-Pyr)] were measured before and after three weeks of treatment with 300 micrograms L-T4/d. T3 and T4 significantly increased and TSH decreased to almost undetectable levels even when measured with a third generation TSH assay. Markers of bone formation showed variable responses with a small but significant increase in BGP but not in PICP or BAP. In contrast, all parameters of bone resorption increased significantly with a good correlation between D-Pyr excretion and the serum parameter ICTP (r = 0.78, p < 0.0001). These changes in bone-turnover markers were not necessarily paralleled by comparable increments of other markers of tissue thyrotoxicosis (SHBG, pulse rate, VO2), suggesting a variability in tissue sensitivity. These rapid responding parameters, especially in the easily obtainable serum parameter ICTP, might be valuable tools in the evaluation of several states of thyroxine excess.
...
PMID:Markers of bone metabolism during short-term administration of thyroxine in healthy volunteers. 807 83

The purpose of this study was to investigate two methods for labeling rabbit sex hormone-binding globulin (rSHBG) with non-radioactive material, biotin (B) and europium (Eu3+), in order to obtain stable labeled SHBG and measure in vivo its metabolism and distribution. The obtained half-life values were compared with [125I]rSHBG half-lives. rSHBG was first isolated by immunoaffinity chromatography using an immobilized monoclonal anti-human SHBG (hSHBG) antibody that cross-reacts with rSHBG. This purified rSHBG was labeled by either biotin-X-N-hydroxysuccinimide ester (rSHBG-B), Eu3(+)-diethylenetriaminepentaacetic dianhydride, or Eu(3+)-isothiocyanatobenzyldiethylenetriamine-tetraacetic acid reagents (rSHBG-Eu3+) or by 125I using Bolton and Hunter reagent ([125I]rSHBG). The labeling procedure preserved the main properties of native SHBG: interaction with the lectine concanavaline A-Sepharose, recognition by anti-hSHBG monoclonal antibody, and, although lower than in native SHBG, the binding affinity for 5 alpha-dihydrotestosterone. These characteristics were the prerequisite for reliable measurement of the metabolism of labeled SHBG. Labeled rSHBG was injected into various rabbits with blood sampling at 2 min and at 1, 2, 4, 8, 12, 24, 48, 72, and 96 h after injection. rSHBG-B or desiaylated rSHBG-B and rSHBG-Eu3+ were captured from serum samples by tubes coated with anti-hSHBG antibody prior to the following detection procedure: biotin was detected by luminometry with the [streptavidin-alkaline phosphatase-dioxetane (AMPPD)] system and europium by time-resolved fluorimetry. [125I]rSHBG was detected by measurement of radioactivity either directly on serum or after fixation on concanavaline A-Sepharose.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Use of non-radioactive labels for half-life measurement of sex hormone-binding globulin in the rabbit. 853 77

The present study was undertaken to determine whether the addition of an androgen to estrogen therapy in postmenopausal women would alter the skeletal response as determined by measurements of markers of bone formation and resorption. Postmenopausal women were treated for 9 weeks with either a combination of 1.25 mg esterified estrogen and 2.5 mg methyltestosterone (E+A) or 1.25 mg conjugated equine estrogen (CEE). Both groups showed a similar decrease in urinary excretion of the bone resorption markers, deoxypyridinoline, pyridinoline, and hydroxyproline. Patients treated with CEE showed decreases in the serum markers of bone formation, bone-specific alkaline phosphatase, osteocalcin, and C-terminal procollagen peptide. In contrast, subjects treated with E+A showed increases in these markers of bone formation. CEE increased, and E+A decreased serum levels of sex hormone-binding globulin as well as triglycerides and high density lipoprotein levels. Only CEE significantly reduced low density lipoproteins. Both regimens were effective in reducing postmenopausal somatic symptoms, but only E+A had a significant effect on psychological symptoms. We conclude that short term administration of androgen with estrogen may reverse the inhibitory effects of estrogen on bone formation. Long term studies are needed to determine the relative benefits and risks of the combination of estrogen and androgen and whether this results in greater increases in bone mass and strength.
...
PMID:Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. 855 Jul 80

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.
...
PMID:Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women. 888 38

We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward's triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L-T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n = 5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter (n = 3). Patients were followed at our institution and treated with the minimal amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14 men (41.2%). The mean daily dose of L-T4 was 172 +/- 6 microg, and the cumulative dose of L-T4 was 673 +/- 71 mg. We found no significant difference between patients and age- and weight-matched controls in BMD (g/cm2) at any site of measurement (lumbar spine 1.144 +/- 0.12 vs. 1.168 +/- 0.15; femoral neck 0.979 +/- 0.13 vs. 1.001 +/- 0.13; Ward's triangle 0.854 +/- 0.17 vs. 0.887 +/- 0.15; and trocanther 0.852 +/- 0.13 vs. 0.861 +/- 0.13). BMD was not correlated with the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and osteocalcin were slightly but significantly elevated in patients compared with controls, whereas there was no difference in intact parathyroid hormone, bone alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone action). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion, has no significant effects on bone metabolism and bone mass in men.
...
PMID:Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine. 924 Jul 28

The objectives of this study were to 1) study the GH-insulin-like growth factor (IGF) axis in adult untreated Turner's syndrome compared to that in age-matched controls; 2) examine the effects of sex hormone substitution on this axis, 3) study the effects of route of administration of 17 beta-estradiol on the measured variables, and 4) examine the effects of sex steroids on hepatic function in Turner patients. Twenty-seven patients with Turner's syndrome were evaluated before and during sex hormone replacement, and an age-matched control group (n = 24) was evaluated once. Main outcome variables were GH and other measures of the GH-IGF axis, body composition, maximal oxygen uptake, sex hormone-binding globulin, and hepatic enzymes and proteins. The integrated 24-h GH concentration (IC-GH; micrograms per L/24 h) was reduced in women with Turner's syndrome (T) compared to controls [C; mean +/- SD, 18.3 +/- 12.0 (T) vs. 37.2 +/- 29.7 (C); P = 0.007]. However, multiple regression revealed that fat-free mass (FFM) and maximal oxygen uptake were significant explanatory variables (joint r = 0.77; P < 0.0005), accounting for 60% of the variance in the 24-h IC-GH. This association was also present in controls. After adjustment for these two variables, any difference in GH concentration between Turner patients and controls disappeared. Serum IGF-I and IGF-II were identical in Turner patients and controls despite the difference in 24-h IC-GH. The level of GH-binding protein (GHBP; nanomoles per L) was higher in Turner women [1.87 +/- 0.72 (T) vs. 1.22 +/- 0.33 (C); P = 0.0005]; after adjustment for FFM, the difference in GHBP levels disappeared between Turner patients and controls. During sex hormone treatment a significant increase was seen in the 24-h IC-GH (P = 0.02), FFM (percentage of weight; P < 0.0005) and maximal oxygen uptake (milliliters of O2 per kg/min; P = 0.02). Serum IGF-I was unchanged, whereas serum IGF-II (micrograms per L) decreased significantly [Turner, basal (TB), vs. Turner, treatment (TT), 860 +/- 135 vs. 823 +/- 150; P = 0.04]. Alanine aminotransferase (units per L), gamma-glutamyl transferase (units per L), and alkaline phosphatase (units per L) were significantly elevated during the basal study period, and all decreased during treatment [alanine amino-transferase, 55 +/- 55 (TB) vs. 30 +/- 20 (TT; P = 0.006); gamma-glutamyl transferase, 92 +/- 98 (TB) vs. 43 +/- 65 (TT; P = 0.003); alkaline phosphatase, 211 +/- 113 (TB) vs. 175 +/- 54 (TT); P = 0.06]. The route of administration of 17 beta-estradiol did not affect its actions. In conclusion, we found the GH-IGF axis in Turner's syndrome to be normal, with body composition and physical fitness exerting the same modifying effects on this axis as seen in the normal population. Sex hormone replacement in Turner's syndrome is associated with normalizing effects on the GH-IGF axis, body composition, physical fitness, and hepatic function. The lowering of hepatic enzymes is a surprising and hitherto undiscovered action of sex steroids. Finally, the route of administration of 17 beta-estradiol is of minor importance in Turner's syndrome.
...
PMID:Body composition and physical fitness are major determinants of the growth hormone-insulin-like growth factor axis aberrations in adult Turner's syndrome, with important modulations by treatment with 17 beta-estradiol. 925 36

Osteoporosis is a major health problem. Little is known about the risk factors in premenopause. Sixty 40-50-year old patients with regular menses were studied cross-sectionally. None of the patients were on drugs known to interfere with bone mass. Patients answered a dietary inquiry and had their bone mineral density (BMD) measured. The Z scores were used for the comparisons. A blood sample was taken for the determination of FSH, SHBG, estradiol, testosterone, calcium and alkaline phosphatase. Calcium and creatinine were measured in 24-h urine. A Z score less than -1 was observed for the lumbar spine of 14 patients (23.3%), and for the femur of 24 patients (40%). Patients with a Z score less than -1 for the lumbar spine were older than patients with a Z score > or = -1 (45.7 vs 43.8 years) and presented higher values of alkaline phosphatase (71.1 +/- 18.2 vs 57.1 +/- 14.3 IU/l). Multiple regression analysis showed that a lower lumbar spine BMD was associated with higher values of alkaline phosphatase, lower calcium ingestion, a smaller body mass index (BMI), less frequent exercising, and older age. The patients with a Z score less than -1 for the femur were shorter than patients with a Z score > or = -1 (158.2 vs 161.3 cm). Multiple regression analysis showed that a lower femoral BMD was associated with lower BMI, higher alkaline phosphatase and caffeine intake, and less frequent exercising. A lower than expected BMD was observed in a significant proportion of premenopausal women and was associated with lower calcium intake, relatively lower physical activity and lower BMI. We conclude that the classical risk factors for osteoporosis may be present before ovarian failure, and their effect may be partly independent of estrogen levels.
...
PMID:Risk factors for decreased bone density in premenopausal women. 945 65

Lack of consistent information concerning the pathophysiology of corticosteroid-related bone loss may be due to coexisting independent factors that influence bone mineral density (BMD). For example, the disease being treated may increase bone turnover and cause bone loss, and its severity may influence the dose of corticosteroids chosen. Similarly, disease remission due to the treatment or disease progression despite treatment may influence bone turnover and the rate of bone loss. The hormonal changes purportedly responsible for reduced bone formation or increased bone resorption may be the result of the disease, not the corticosteroids. To determine the pathophysiology of corticosteroid-related bone loss, we conducted a controlled, prospective study in men with no systemic illness treated with corticosteroids to reduce antisperm antibodies. We measured BMD using dual x-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover in 9 men before and during prednisolone treatment and in 10 age-matched controls. The results were expressed as the mean +/- SEM. There were no differences in BMD between the two groups at baseline. The patients received 50 mg prednisolone daily for 3.7 +/- 0.6 months (range, 1-6). BMD decreased by 4.6 +/- 0.8% at the lumbar spine (P = 0.0007), by 2.6 +/- 0.6% at the trochanter (P = 0.004), and by 4.8 +/- 1.9% at the Ward's triangle (P < 0.04). The decrease in lumbar spine BMD correlated with the cumulative dose of corticosteroids (r = -0.49; P = 0.03). Serum osteocalcin and skeletal alkaline phosphatase decreased by 28.5 +/- 15.5% (P = 0.08) and 24.2 +/- 8.6% (P < 0.03), respectively. The decrease in lumbar spine BMD correlated with the decrease in osteocalcin (r = -0.48; P < 0.02). Serum testosterone and sex hormone-binding globulin decreased by 28.6 +/- 4.4% (P < 0.003) and 28.5 +/- 8.3% (P < 0.007), respectively. The testosterone/sex hormone-binding globulin ratio did not change. The decrease in total testosterone correlated with the decrease in osteocalcin (r = -0.40; P = 0.05). There were no detectable changes in urinary C-telopeptide, serum PTH, or serum calcium. Estradiol decreased by 23.5 +/- 11.4% (P < 0.003). Corticosteroid therapy results in rapid bone loss, probably due to reduced bone formation. Neither increased bone resorption nor secondary hyperparathyroidism appears to contribute to the rapid bone loss. Whether the reduction in bone formation may be partly mediated by changes in sex steroids remains unclear.
...
PMID:Corticosteroid-induced bone loss in men. 950 31


1 2 3 4 Next >>

---