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

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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)

The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and a combination of OCPs and GnRH-a in the treatment of hirsute women (modified Ferriman-Gallwey score 10), 20-39 years old, was compared and the impact of these treatments on hormonal and Ca metabolism was investigated. 33 women were prospectively enrolled and randomized into 3 treatment groups (11 in each group): 1) OCPs [35 mcg ethinyl estradiol plus 1 mg norethindrone administered cyclically]; 2) GnRH-a, 3.75 mg im, every 4 weeks for 24 weeks; or 3) a combination of both OCPs and GnRH-a at the above doses taken concurrently. All medications were administered for 6 months. The serum levels of LH, estradiol, testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone declined in all 3 treatment groups. The assessment of hirsutism by the Ferriman-Gallwey score revealed a similar 25% reduction in score by all 3 treatment groups by 6 months. The symptoms of hot flashes and vaginal dryness were greatest in subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased significantly in subjects treated with the GnRH-a alone. In the OCP groups there was significant decline in serum Ca from baseline to 24 weeks (p or = 0.01). There was significant urinary loss of Ca in the GnRH-a group with respect to 24-hour excretion (p or = 0.001). The estimated Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups, however, it declined by 90 mg/day from baseline in the GnRH-a-treated women from 111 +or- 43 to 21 +or- 58 mg/day (p or = 0.001). Bone density significantly decreased (by 2.7%) in the lumber spine in women treated with GnRH-a alone (p or = 0.02), with a less marked decline in the femoral neck. The negative impact of GnRH-a alone on Ca balance and bone loss limits its usefulness as a single agent for long-term therapy of hirsutism.
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PMID:Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study. 771 86

Between June 1988 and March 1989 in Italy, health workers enrolled 200 women aged 19-23 attending obstetric-gynecology clinics in and around Pavia into a five-year study of the effects of an oral contraceptive (OC) with 20 mcg ethinyl estradiol and 0.15 mg desogestrel on bone mass. They were able to follow 76 of the 100 women using the OC and 71 of the 100 women using no OC for five years. Health workers conducted a bone mass density (BMD) evaluation at spinal level L2-L4 with Dexa (Norland XR-26). They measured serum alkaline phosphatase levels and urinary excretion of hydroxyproline (OH-proline) at baseline and every 12 months for five years. Neither urinary excretion of OH-proline levels nor alkaline phosphatase levels differed significantly in the two groups during the five years from baseline levels. Over the five years, the BMD of OC users did not change significantly while the BMD of the controls increased 7.8% from baseline (p 0.01). These findings suggest that this monophasic OC prevented or delayed the physiologic peak bone mass. Even though the low dosage of ethinyl estradiol (20 mcg) may have contributed to the prevention of bone mass loss, it could not achieve the peak bone mass. More studies are needed to understand the effect of long-term OC treatment on bone mineral content.
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PMID:Bone mass and long-term monophasic oral contraceptive treatment in young women. 779 86

DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) in a ratio of 100:7, was administered orally to rats for 14 days in order to investigate a possible origin of the increased serum alkaline phosphatase (ALP). Increased serum total ALP was noted in rats receiving DT-5061 at 5.35 mg/kg/day or EE at 0.35 mg/kg/day. Electrophoresis of serum ALP revealed that both liver and bone-type ALP isozymes were increased in the DT-5061 5.35 mg/kg and EE 0.35 mg/kg groups, and the ratio of increase in the liver-type was greater than that in the bone-type although the increase in concentration of the bone-type was greater as compared to the liver-type. ALP level in the liver was elevated together with an increase in liver weight, consistently with the increased serum liver-type isozyme. However, neither histological changes indicative of cholestasis nor increase in serum leucine aminopeptidase, bilirubin, GOT or GPT were seen. No changes were observed in bone ALP activity; hence inconsistent with the increased serum bone-type isozyme. From these results, it is considered that the increased serum ALP induced by this drug was due to the increased liver-type isozyme induced in the liver and to the increased bone-type isozyme, and among the ingredients of this oral contraceptive, EE was mainly involved in the increased serum ALP induced by this drug.
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PMID:[Increased serum alkaline phosphatase induced by DT-5061, an oral contraceptive, in rats]. 783 3

DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) was administered orally to adrenalectomized rats for 3 days to investigate involvement of the adrenals in the increased serum alkaline phosphatase (ALP). In addition, corticosterone or aldosterone were administered to the adrenalectomized rats to examine their effects on serum ALP. Increases in serum total ALP, liver-type and bone-type ALP isozymes were observed in rats with intact adrenals following administration of DT-5061, but these responses were not noted in adrenalectomized rats. Increases in liver weight and ALP activity in the liver after administration of the drug were reduced but not abolished in the adrenalectomized rats. The adrenalectomized rats receiving corticosterone showed increases in serum total ALP, liver-type ALP isozyme and liver weight but did not exhibit any increase in bone-type ALP isozyme. On the other hand, aldosterone did not increase and even reduced serum ALP although ALP activity in the liver was increased in the adrenalectomized rats.
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PMID:[Effects of adrenalectomy on the increased serum alkaline phosphatase activity induced by DT-5061, an oral contraceptive, in rats]. 783 4

Estrogen replacement therapy (ERT) prevents bone loss and fracture in early postmenopausal women, but its benefit for women over 70 yr of age has not been determined. We have examined the effect of a short course of ERT on biochemical markers of bone turnover in older women. Eleven women (mean age, 77 yr) were given conjugated estrogen (Premarin; 0.625 mg/day) for 6 weeks. Biochemical markers were measured on serum and urine collected at baseline (two samples), after 5 and 6 weeks of ERT, and 5 and 6 weeks post-ERT. Markers of bone formation were osteocalcin, bone alkaline phosphatase, and type I procollagen peptide. Markers of bone resorption were total urinary hydroxyproline, total and free pyridinoline and deoxypyridinoline cross-links, type I collagen cross-linked N-telopeptides, and serum C-terminal cross-linked telopeptide. Data were analyzed by repeated measures multivariate analysis of variance to estimate the overall effect of ERT on the biochemical markers. Markers of bone resorption decreased during ERT and returned to baseline after ERT (P < 0.05). Markers of bone formation declined less during ERT and continued to decline after ERT (P < 0.05). We conclude that ERT reduces bone turnover in older women and that markers of bone turnover may be useful in assessing the response to treatment in this age group.
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PMID:The short-term effects of conjugated estrogen on bone turnover in older women. 804 49

Estrogen/gestagen replacement therapy prevents excess bone loss in postmenopausal women. The mode of action by which these sex steroids exert their anabolic effects on bone has not been completely clarified yet. In this study, 17 beta-estradiol (E2), as well as progestins progesterone (P), dydrogesterone (DD), 20 alpha-dihydroxydydrogesterone (DHD), medroxyprogesterone acetate (MPA), and cyproterone acetate (CPA) were able to stimulate the mitogenesis and differentiation of normal adult human osteoblast-like (HOB) cells harvested from female trabecular bone explants. The different progestins exerted a more pronounced stimulatory effect on HOB proliferation than E2 did. The combination of E2 with P, DD, or DHD did not result in a statistically significant further increase of HOB proliferation, as compared with the progestins alone. In general, E2 showed a stronger differentiation-inducing effect than the progestins, as measured by histochemical staining of the HOB cells for alkaline phosphatase activity. Combining E2 and the progestins did not result in a further increase of the number of alkaline phosphatase positive cells, compared with E2 alone. The different progestins proved to be equally potent in stimulating HOB proliferation and differentiation. In conclusion, progestins as well as E2 exerted anabolic but differential effects on normal adult human osteoblasts in vitro.
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PMID:A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro. 806 52

Estrogens play an important but poorly understood role in the maintenance of skeletal mass. Whereas the mechanisms of estrogen action on bone may be complex, the finding that osteoblasts express estrogen receptors suggests that this class of hormones exerts direct effects on bone cells. To understand how estrogens regulate osteoblastic function, the physiologically active estrogen metabolite 17 beta-estradiol was tested to determine its effects on the well characterized murine osteoblastic cell-line MC3T3-E1. Experiments were designed to identify the effects of estrogen on osteoblastic activities associated with both the formation and the resorption of bone. Estrogen treatment coordinately increased DNA content and alkaline phosphatase activity in MC3T3-E1 cells as much as twofold. The stimulatory effect on alkaline phosphatase was stereospecific, dose-dependent between 0.1 and ten nanomolar, and dependent on the time in culture when the hormone was administered. The effect was also persistent, since alkaline phosphatase activity remained elevated for several days after withdrawal of the hormone. Estrogen increased the levels of messenger RNA for alkaline phosphatase and type-I collagen as well, and these effects also persisted after removal of the hormone. The levels of messenger RNA for osteopontin, another bone-matrix protein, were only slightly affected by estrogen. Finally, estrogen inhibited the activation of adenylate cyclase by three osteotropic agents known to stimulate the resorption of bone: parathyroid hormone, prostaglandin E2, and the beta-adrenergic agonist isoproterenol. Thus, estrogen promoted the expression of traits associated with the formation of bone while reducing cellular responsiveness to hormones that may trigger the resorption of bone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct modulation of osteoblastic activity with estrogen. 817 20

Serum bone Gla protein (BGP) and alkaline phosphatase (AP) activity were compared for the assessment of skeletal status in 11 normal pregnant women, 12 normal women on days 3 and 13 of the menstrual cycle, five postmenopausal women before and after 1 month of treatment with ethinyl estradiol (20 micrograms/day), five patients with cancer and hypercalcemia during treatment with calcitonin, and one patient with Paget disease during treatment with Plicamycin. BGP and AP correlated with each other only in the pregnant women. In all other circumstances, there was no correlation between these two serum osteoblast products. Furthermore, there were conditions in which the two measurements became discordant. These studies demonstrate that BGP and AP commonly are dissociated when used as measurements of skeletal status. Although both are osteoblast products, BGP and AP probably reflect different aspects of osteoblast differentiation and function.
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PMID:Associations and dissociations between serum bone Gla protein and alkaline phosphatase in skeletal metabolism. 841 Apr 67

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.
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PMID:Follow-up of bone mineral density in 27 cases of anorexia nervosa. 898 Jan 62

Estrogen (E2) has been shown to prevent bone loss among postmenopausal women. The molecular mechanism(s) by which this is accomplished is not clear. The discovery of E2 receptor (ER) in osteoblasts and osteoclasts has implicated these cells as direct targets for E2. Previous studies on the effects of E2 on osteoblastic cells in vitro or in organ culture present conflicting results, possibly due to heterogeneity in cell types, stage of differentiation, ER levels, and/or species differences. The effects of E2 on gene expression during various stages of human osteoblast cell differentiation has not been investigated extensively. In this study we employed a newly developed human fetal osteoblastic cell line (hFOB/ER9) that contains high levels of ER to examine the effects of E2 on osteoblast proliferation and differentiation. The basal levels and E2 effects on the expression of various extracellular matrix proteins were also characterized throughout different stages of differentiation. These stages include a proliferative/relatively undifferentiated stage (day 6), a matrix maturation stage (days 10-14), and a mineralization/calcified nodule stage (day 18). During the stage of rapid cell proliferation, E2 treatment of hFOB/ER9 cells resulted in a dose-dependent decrease in [3H]thymidine incorporation to a maximum of 72% compared to the vehicle control value. Treatment of hFOB/ER9 cells with 10(-9) M E2 for 48 h resulted in an increase in alkaline phosphatase (AP) activity throughout cell differentiation. The magnitude of AP induction varied from approximately 200-500%. In contrast, E2 decreased osteocalcin protein levels to a minimum of 54% compared to the vehicle control value. The steady state messenger RNA levels for AP increased and osteocalcin decreased after E2 treatment, similar to the responses observed at the protein level. At all stages, there was little or no effect of E2 on type I collagen protein levels or osteonectin steady state messenger RNA levels. The E2 responses on hFOB/ER9 cell matrix protein expression and cell proliferation were mediated through the ER, as cultures cotreated with a 100-fold molar excess of a type II anti-E2 (ICI 182,780) abrogated these effects. These results support the hypothesis that E2 does have an effect on osteoblastic differentiation by decreasing hFOB/ER9 cell proliferation and differentially regulating extracellular matrix expression.
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PMID:Estrogen regulation of human osteoblastic cell proliferation and differentiation. 920 36


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