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)

An enzyme-linked immunosorbent assay (ELISA) of the "sandwich-type" for sex hormone binding globulin (SHBG) has been developed. A rabbit anti-SHBG antibody (RAb) is immobilized to the microtitre plate. After incubation with standards and samples a second monospecific rabbit anti-SHBG antibody, labelled with alkaline phosphatase is added (RAb). Following further washing substrate is added, colour developed and the plate read at 405 nm wavelength on a standard ELISA plate reader. The assay is not influenced by the presence of steroids at the binding site, and shows good agreement to SHBG binding capacity assay and commercially available IRMA. Its sensitivity, specificity and precision allows its use in the routine laboratory. The SHBG ELISA has been used to measure SHBG concentrations in sera of normal men, women, pregnant women, and women receiving high-dose medroxyprogesterone acetate as a treatment of metastatic breast cancer.
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PMID:An enzyme-linked immunosorbent assay (ELISA) for human sex hormone-binding globulin. 296 47

To investigate the efficacy of transdermal dihydrotestosterone therapy on 22 patients with microphallus, we applied dihydrotestosterone gel for 8 weeks to the external genitalia at daily doses of 12.5 mg. and 25 mg. for ages less than and older than 10 years, respectively. All patients were evaluated for penile and prostatic growth, pituitary-gonadal axis function, serum sex hormone binding globulin, lipid metabolism, hepatotoxicity, bone age and height velocity. All patients demonstrated growth of the penis during treatment. The mean increase rate (153%) in the first 4 weeks of treatment was higher than that (118%) of the second 4 weeks. Of importance is that responses were noted in 4 patients who had failed testosterone therapy for microphallus. The pituitary-gonadal axis was transiently suppressed during treatment, and serum sex hormone binding globulin and lipid metabolism were transiently affected during treatment. Serum alkaline phosphatase increased, mainly due to change of bone isoenzyme but bone ages and mean height velocity were not significantly affected. In conclusion, transdermal dihydrotestosterone therapy is an effective and relatively safe modality in the treatment of microphallus.
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PMID:Transdermal dihydrotestosterone therapy and its effects on patients with microphallus. 832 17

To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density (BMD) in elderly women, BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry, in 330 healthy women aged 70 and over. Vitamin D metabolites, sex hormone binding globulin (SHBG), PTH(1-84), osteocalcin, alkaline phosphatase, and hydroxyproline and calcium excretion in 2 h fasting urine were measured. Multiple linear regression was used to adjust for potential confounders. In 65% of the women, serum 25(OH)D was below 30 nmol/l. Only values below a threshold for 25(OH)D were negatively related to serum PTH(1-84) (p = 0.02, threshold at 25 nmol/l) and to osteocalcin levels (p = 0.04, threshold at 30 nmol/l). BMD of the femoral neck and trochanter was positively related to serum 25(OH)D (left neck p = 0.001) with thresholds at 30 nmol/l whereas the distal radius was not (p = 0.32). Serum PTH was negatively related to BMD at all measurement sites (all p < 0.001). Serum SHBG, an inverse measure of estrogen activity, was positively related to osteocalcin levels (p = 0.004) and the urinary hydroxyproline/creatinine ratio (p = 0.002) and negatively related to the BMD of the trochanter (left trochanter p = 0.02) and the distal radius (p = 0.001). We conclude that in elderly women, serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover. SHBG is positively related to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. 858 20

This study was performed on 19 postmenopausal female volunteers in a period of five months of moderate physical exercise in order to examine beneficial changes in muscle strength and flexibility as well as changes in sex hormone binding globulin (SHBG) and other parameters related to bone metabolism. While SHBG decreased significantly (from 56.0 +/- 20.0 to 43.9 +/- 16.1 nM, P = 0.009) phosphorus and urea increased (from 2.8 +/- 0.4 to 4.0 +/- 0.5 mg/dl, P = 0.00006 and from 32.1 +/- 9.4 to 42.3 +/- 11.0 mg/dl, P = 0.03, respectively). These changes were accompanied by significant increases in muscle strength and flexibility. Other parameters such as alkaline phosphatase and calcium did not change significantly during the study. Plasma levels of SHBG were negatively correlated with phosphorus. As higher SHBG has been related to increased bone loss in older women, we conclude that moderate physical activity is an effective means to preserve bone loss in postmenopausal women.
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PMID:Effects of physical exercise on some parameters of bone metabolism in postmenopausal women. 879 92

A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0 +/- 3.3 years, mean menopause duration 20.4 +/- 5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at -20 degrees C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was -1.41% (0.18) at the lumbar spine and -0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.
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PMID:Can biochemical markers predict bone loss at the hip and spine?: a 4-year prospective study of 141 early postmenopausal women. 893 Oct 35

There is no established treatment for osteoporosis in men, a common and disabling condition the incidence of which is increasing rapidly. We conducted an open study to investigate the efficacy and mode of action of testosterone therapy in eugonadal men with osteoporotic vertebral crush fracture. Twenty-one men, aged 34-73 (mean 58), were treated with intramuscular testosterone esters (Sustanon 250) every 2 weeks for 6 months. Bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry was performed at baseline and 6 months. We also measured biochemical markers of bone turnover, testosterone, estradiol, sex hormone binding globulin (SHBG), and gonadotrophins at baseline and after 3 and 6 months of treatment. Treatment was well tolerated, and side effects were uncommon. Lumbar spine BMD increased by 5% from 0.799 to 0.839 g/cm2 (p < 0.001). All bone markers decreased, indicating that treatment suppressed bone turnover. Although serum osteocalcin levels fell only slightly, there were large reductions in urinary deoxypyridinoline and N-telopeptide (p < 0.05), which were correlated with the increase in spinal BMD. Interpretation of the findings with other markers, such as bone-specific alkaline phosphatase and pyridinoline, was confounded by the wide scatter of values. Serum testosterone increased by 55%, while SHBG decreased by 20%, leading to a rise in free androgen of 90%. Serum estradiol also increased by 45%. The change in spine BMD was significantly correlated with a change in serum estradiol but not with a change in serum testosterone. We therefore conclude that testosterone is a promising treatment for men with idiopathic osteoporosis, acting to suppress bone resorption by a mechanism that may involve estrogen.
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PMID:Androgen supplementation in eugonadal men with osteoporosis: effects of six months' treatment on markers of bone formation and resorption. 907 91

Biochemical markers of bone turnover can be used to study the pathophysiology of osteoporosis. So far there have been few such studies in men. The aims of this study were to determine the effect of aging on bone turnover and to identify which hormones might regulate bone turnover in men. We studied 178 healthy Caucasian men, ages 20-79 years (30 per decade). The data for the effect of age on bone turnover was best fit by a quadratic function (nadirs at age 56, 57, 53, 39, and 58 years for intact propeptide of type I procollagen, osteocalcin, bone alkaline phosphatase, free deoxypyridinoline, and cross-linked N-telopeptides of type I collagen, respectively). For most markers, bone turnover tended to be highest in the third decade, lowest in the fifth and sixth decade, with a small increase in some markers in the eighth decade. Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3, dehydroepiandrosterone sulfate, testosterone, estradiol, and free androgen index all decreased significantly with age (54, 17, 76, 26, 33, and 57%, respectively), while sex hormone binding globulin and parathyroid hormone increased significantly with age (62% and 43%). IGF-I and sex hormones were positively correlated with bone turnover, and this association was stronger in young men than older men. In conclusion, increased IGF-I and sex hormones may be associated with increased bone turnover in young men, with less influence on bone turnover in older men.
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PMID:Age-related changes in bone turnover in men. 1040 22

In a prospective study of 348 apparently healthy women, aged 70 years and over (mean 80.3 years), we examined bone mineral density (BMD), biochemical markers of bone metabolism, and some easily measurable predictors in relation to hip and osteoporotic fractures. In addition, we constructed risk profiles for hip and osteoporotic fractures. At baseline, BMD at both hips, using dual-energy X-ray absorptiometry, body height and body weight were measured. At the same time, serum and urine samples were obtained for biochemical analysis. Serum samples were analyzed for vitamin D metabolites, sex hormone binding globulin, serum intact parathyroid hormone, osteocalcin, alkaline phosphatase, phosphate, albumin, calcium and creatinine. In 2 h fasting urine, hydroxyproline, type I collagen crosslinked N-telopeptide (NTx) and calcium excretion were measured. Furthermore, easily measurable predictors, such as previous fracture, body mass index (BMI) and mobility were assessed. During the follow-up period (mean duration 5.0 years), hip and any osteoporotic fracture (wrist, humerus or hip fracture) occurred in 16 and 33 participants, respectively. Data were analyzed using Cox regression analysis. BMD of the trochanter (per 1 SD decrease) and previous fracture were most strongly associated with hip fractures (adjusted relative risk (RR) = 3.0, 95% confidence interval (CI): 1.4-6.6; RR = 4.2, 95% CI: 1.5-11.6, respectively) and osteoporotic fractures (RR = 1.8, 95% CI: 1.1-2.8; RR = 2.9, 95% CI: 1.5-5.7, respectively). Previous fracture, BMI and mobility were identified as easily measurable predictors for hip fractures, whereas previous fracture, use of loop diuretics and age were predictors for osteoporotic fractures in the risk profile model. The risk of fractures can be predicted with three easily measurable predictors. This study confirms the importance of previous fracture as a predictor for hip fractures and other fractures. It also shows that the use of loop diuretics is a predictor for osteoporotic fractures.
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PMID:Predictors of fractures in elderly women. 1079 71

The cause of age-related bone loss in men is poorly understood. Previous studies of the relationship between bone density and serum androgens have yielded inconsistent results, perhaps partly because age is a determinant of both. Recent studies suggest that serum estrogen levels influence bone density in adult men. In order to determine whether bone mineral density (BMD) and bone turnover are associated with serum sex steroids, we investigated 37 normal men within a narrow age range (60-70 years). Bone mineral density at the forearm, hip, and spine, testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI:T/SHBG), estradiol (E), free estradiol index (FEI:E/SHBG), and markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type I C-terminal extension peptide) and bone resorption (hydroxyproline/creatinine [OHPr/Cr], deoxypyridinoline/creatinine [Dpd/Cr], pyridinoline/creatinine, collagen type I cross-linked telopeptide) were measured. Bone mineral density was positively related (r > 0.35, p < 0.05 at all sites) to log FAI, whereas there was no significant relationship between BMD and either serum total testosterone, serum E, or FEI. Bone density at the spine and hip were inversely related to both OHPr/Cr (r > -0.41, p < 0.05 for all sites) and Dpd/Cr (r > -0.36, p < 0.05 for all sites). OHPr/Cr (r = -0.41, p < 0.05) and Dpd/Cr (r = -0.41, p < 0.05) were both inversely related to log FAI. We conclude that BMD and bone turnover in adult men are related to plasma free androgens.
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PMID:The relation between bone density, free androgen index, and estradiol in men 60 to 70 years old. 1086 22

Idiopathic hirsutism is relatively uncommon, affecting approximately 6% of hirsute women. In the present study we compared the bone mineral density (BMD) of women with idiopathic hirsutism with controls. A group of 20 women diagnosed with idiopathic hirsutism was evaluated with respect to BMD and the findings were compared to those of a control group consisting of 10 normal women. Hirsutism was graded according to the Ferriman-Gallwey score and threshold was considered to be a score more than 4. There was no statistically significant difference with respect to patients' mean age, BMI and body fat composition. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), androstenedione, testosterone, free testosterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG) and estradiol were assessed in both groups and no statistically significant differences were found. There was no statistically significant difference with respect to bone turnover--which was evaluated by determining the serum levels of parathyroid hormone, calcium, alkaline phosphatase and osteocalcin as well as the urinary secretion of calcium and hydroxyproline, corrected for the creatinine values--between the two groups. Statistical analysis was performed using the t test for unpaired data to compare age, BMD and biochemical data, and Wilcoxon's rank test was used to compare physical activity and calcium intake. Statistical significance was defined as p < 0.05. The BMD at the level of the 2nd to 4th lumbar vertebrae (L2-L4) and the total BMD were higher in women with idiopathic hirsutism compared to those in the control group, suggesting a possible direct effect of androgens on the osseous tissue of hirsute women.
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PMID:Bone mineral density in women with idiopathic hirsutism. 1110 75


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