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)

Administration of GnRH agonist analogs to women may result in a hypoestrogenic state and bone mass reduction. In the present study we examined bone mineral density (BMD) and parameters of mineral metabolism in elderly men with benign prostatic hyperplasia before and during a hypoandrogenic state induced by the long-acting GnRH agonist D-Trp6-LHRH (decapeptyl). Our results showed that decapeptyl treatment caused a significant decrease in serum testosterone concentrations in all patients and resulted in a significant decrease in individual vertebral BMD in 10 of 17 patients. A significant decrease in BMD was observed in 5 patients after 6 months of treatment. Another 5 patients showed a decreased BMD only after 12 months. The mean serum concentrations of osteocalcin, phosphorus, and alkaline phosphatase activity increased after 6-12 months of treatment with decapeptyl. Serum calcium, vitamin D metabolites, and PTH concentrations remained unchanged during treatment. Urinary calcium excretion was slightly, but not significantly, increased after 6 months of treatment. These results demonstrate that long-acting GnRH agonist treatment may cause high turnover accelerated bone loss in some men during the first year of GnRH agonist treatment, as has been previously shown in women.
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PMID:Decreased bone density in elderly men treated with the gonadotropin-releasing hormone agonist decapeptyl (D-Trp6-GnRH). 767 97

Suppression of androgen levels of stage D2 prostate cancer patients has been the prominent treatment for advanced prostate cancer. An arithmetic formula expressing disease aggressivity computed by the pre-treatment levels of alkaline phosphatase (AP), degree of tumor differentiation and number of bone metastases correlated well with disease response and outcome in stage D2 patients treated by chronic administration of the gonadotropin-releasing hormone agonistic analogues (GnRH-As; buserelin) or orchiectomy. In the present study we analyzed retrospectively disease response and outcome in 262 previously untreated stage D2 prostate cancer patients who received combination hormonal treatment (GnRH-A plus flutamide) using this aggressiveness score. Mean value of this aggressiveness score between patients who were grouped with reference to type of disease response according to the criteria established by the National Prostatic Cancer Project (NPCP) was statistically different (Kruskal-Wallis, p > 0.001). Pairwise comparison documented that this was true between all but the stable and progression groups. Linear regression analysis documented significant correlation of this aggressiveness score with length of response and survival (r = 0.59, and 0.45, respectively: p > 0.0001). Analysis of slopes obtained by linear regressions between aggressiveness score and survival in patients treated with GnRH-A plus flutamide and with GnRH-A monotherapy documented that disease response and outcome was superior among patients who received combination hormonal treatment. These data indicate that this aggressiveness score correlated well type of disease response, length of response, and survival with patients given combination hormonal treatment, and as such it can be used as an objective tool for analyzing clinical data.
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PMID:Stratification of stage D2 prostate cancer patients by a disease aggressiveness score and its use in evaluating disease response and outcome to combination hormonal treatment (GnRH-A plus flutamide). 801 Jul 19

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.
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PMID:Prognostic factors of advanced prostatic carcinoma. 829 78

Treatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced bone turnover and accelerated bone loss in premenopausal women with endometriosis, uterine leiomyomatomas and hirsutism. Sodium etidronate is a powerful inhibitor of bone resorption which had been proven efficacious in the prevention and treatment of postmenopausal osteoporosis. The objective of this study was to evaluate the skeletal effects of 6 months of therapy with the depot preparation of the GnRH agonist triptorelin (decapeptil 3.75 mg intramuscularly every 4 weeks) in 24 hirsute patients, aged 24-33 years, with hyperandrogenic chronic anovulation. Ten patients also received cyclical etidronate in an oral dose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg/day elemental oral calcium (one cycle). The remaining 14 patients received 500 mg/day of elemental calcium continuously. After 6 months all treatments were discontinued for at least a further 6 months. Bone mineral density (BMD) at lumbar spine and hip (dual-energy X-ray absorptiometry, Sophos LXRA, France) and biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N-telopeptide and hydroxyproline/creatinine ratio) were evaluated at baseline, 6 months and 12 months. In the group given GnRH agonist alone BMD fell significantly at all measured skeletal sites during the first 6 months. In the patients treated with etidronate a significant decrease in BMD was observed at lumbar spine but not in the femoral neck and trochanter, and the changes at lumbar spine and trochanter were significantly smaller than those in the control group. At 6 months bone turnover was also increased in patients treated with GnRH and calcium. Cyclical etidronate prevented the increase in biochemical markers of bone formation and resorption, with the exception of calcium/creatinine excretion, which was significantly increased in both groups. Six months after treatment withdrawal BMD did not recover in either group. Biochemical markers (N-telopeptide, serum alkaline phosphatase) remained increased in those patients previously treated with calcium alone while they remained close to baseline values in the patients treated with cyclical etidronate. Our study indicates that: (1) GnRH agonist therapy causes remarkable bone loss in young individuals with androgen excess who are expected to have increased bone mass; (2) this bone loss can be partially prevented by intermittent cyclical etidronate therapy.
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PMID:Intermittent Etidronate partially prevents bone loss in hirsute hyperandrogenic women treated with GnRH agonist. 916 93

CrossLaps peptide [Glu-Lys-Ala-His-Asp-Gly-Gly-Arg], a part of the C-telopeptide of the alpha 1-chain of type I collagen of bone, is a recently developed biochemical marker of bone turnover. In this study, the clinical utility of measurement of urinary CrossLaps was investigated in eleven premenopausal women who received a gonadotropin-releasing hormone (GnRH) agonist for 6 months for treatment of adenomyosis (n = 1) or leiomyomas (n = 10). Along with urinary CrossLaps, the levels of various biochemical markers, and serum estradiol, calcitonin and intact parathyroid hormone (i-PTH) were measured, and lumbar spine bone mineral density (BMD) was also monitored before, during, and at the end of the course of GnRH agonist therapy. Apart from CrossLaps, markers of bone resorption tested were urinary pyridinoline, deoxypyridinoline and hydroxyproline. Markers of bone formation tested were serum osteocalcin and bone-specific alkaline phosphatase (B-ALP). Serum estradiol levels decreased to undetectable levels at 2 months of GnRH agonist therapy. The values for all biochemical markers increased significantly throughout the therapy. The degree of an increase in CrossLaps levels was greater than that in all other markers. Mean lumbar spine (L2-L4) BMD was decreased by 7.2% at 6 months of treatment. The percent change in BMD at 6 months of treatment correlated inversely with the percent change in CrossLaps levels from the baseline to 1, 2, and 5 months of treatment. These results indicate that measurement of urinary CrossLaps might be a useful tool to predict the risk of bone loss caused by hypoestrogenism including GnRH agonist therapy.
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PMID:Clinical usefulness of urinary CrossLaps as a sensitive marker of bone metabolism. 944 79

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result of the change in the level of monoamines in CNS under Zoladex.
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PMID:Androgen level variations, clinical response to LHRH agonists and changes in the quality of life subscales in metastatic prostate cancer--speculations about possible role of the monoamine system. 947 91

Changes in bone modeling and remodeling in the tibia of growing rats within 30 days of ovariectomy (ovx) were evaluated by histomorphometric, mechanical; and biochemical means. Three days after ovx, suppressed bone formation was seen. This was shown by reduced osteoid volume, osteoblast surface, and bone formation rate in the secondary spongiosa, and a reduced longitudinal growth rate in the growth plate. In addition, the alkaline phosphatase and tartrate-resistant acid phosphatase activity in bone marrow supernatants was suppressed in conjunction with elevated serum sialic acid levels, indicating inflammation. Although estrogen deprivation itself may provoke the inflammatory process, the serum sialic acid level in the ovx group returned to the baseline level within 5 days after surgery, while that of estradiol in the ovx group remained consistently lower. This suggests that surgical stress, not estrogen deprivation, is the primary cause of the inflammatory response shortly after ovx. A significant difference (p < 0.01) between the ovx and sham rats was seen in the osteoclast surface, which peaked on day 7 in the ovx rats. On day 14 postovariectomy, the bone formation rate peaked and remained constant until day 30. In the ovx rats, there was a sustained reduction in the serum albumin level until day 30. Estrogen deprivation may be the primary cause of these changes, because both surgical ovx and medical oophorectomy with gonadotropin-releasing hormone agonist (G(nRHa) reduce the serum albumin level. In numerous studies dealing with changes after ovx in rats, we have observed: 1) a transient reduction in bone formation in relation to inflammatory changes evoked by ovx surgery, and 2) a sustained reduction in the serum albumin level for at least 30 days after ovx that is possibly due to estrogen deprivation.
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PMID:Reduction in bone formation and elevated bone resorption in ovariectomized rats with special reference to acute inflammation. 1061 56

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.
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PMID:Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata. 1068 31

A 78-year-old man admitted with clinical jaundice and pelvic pain had a total bilirubin level of 6.56 mg/dL, an alkaline phosphatase level of 855 U/L, and a prostate specific antigen (PSA) level of 9996 ng/mL. A computed tomogram demonstrated marked retroperitoneal, peripancreatic, periceliac, and periaortic lymphadenopathy. A bone scan revealed increased radiolabeled technetium uptake in the pelvis, vertebral column, parietooccipital region, ribs, and appendiceal skeleton. A biopsy of one pelvic lesion revealed metastatic prostate cancer. This man's obstructive jaundice and bone pain had a dramatic response to treatment with a gonadotropin-releasing hormone analog (leupro lide) and antiandrogen (bicalutamide). All bone pair and clinical signs of jaundice disappeared in 1 week His total bilirubin decreased to 0.84 mg/dL by 2 weeks His PSA values reflected this clinical response, decreasing to 4022 ng/mL in 1 week, 2680 ng/dL after 2 weeks and 1028 ng/mL after 1 month of the above therapy.
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PMID:Metastatic prostate cancer (with prostate-specific antigen of 9996) presenting as obstructive jaundice. 1069 97

More than 80% of human ovarian cancers express LHRH and its receptor as part of a negative autocrine mechanism of growth control. This study was conducted to investigate whether LHRH affects apoptosis in ovarian cancer. EFO-21 and EFO-27 ovarian cancer cells were treated with LHRH agonist Triptorelin or with cytotoxic agent Doxorubicin in the absence or presence of Triptorelin. Apoptotic cells were quantified by flow cytometry. Expression of nuclear factor kappa B (NFkappaB) was assessed by RT-PCR and immunoblotting. For determination of Triptorelin-induced NFkappaB activation, cells were transfected with a NFkappaB-secreted alkaline phosphatase reporter gene plasmid (pNFkappaB-SEAP) and cultured for 96 h with or without Triptorelin. The causal relation between Triptorelin-induced NFkappaB activation and Triptorelin-induced protection against apoptosis was investigated using SN50, an inhibitor for nuclear translocation of activated NFkappaB. Apoptosis induction by Triptorelin was never observed. Treatment with Doxorubicin (1 nmol/L) for 72 h increased the percentage of apoptotic cells in EFO-21 and EFO-27 ovarian cancer cell lines to 31% or 34%, respectively. In cultures treated simultaneously with Triptorelin (100 nmol/L), the percentage of apoptotic cells was reduced significantly, to 17% or 18%, respectively (P < 0.001). RT-PCR and immunoblotting experiments showed that NFkappaB subunits p50 and p65 were expressed by ovarian cancer cell lines EFO-21 and EFO-27. When EFO-21 or EFO-27 cells were transfected with pNFkappaB-SEAP and subsequently treated with Triptorelin (100 nmol/L), NFkappaB-induced SEAP expression increased 5.3-fold or 4.7-fold, respectively (P < 0.001). Triptorelin-induced reduction of Doxorubicin-induced apoptosis was blocked by SN50-mediated inhibition of NFkappaB translocation into the nucleus. We conclude that LHRH induces activation of NFkappaB and thus reduces Doxorubicin-induced apoptosis in human ovarian cancer cells. This possibility to protect ovarian cancer cells from programmed cell death is an important feature in LHRH signaling in ovarian tumors, apart from the inhibitory interference with the mitogenic pathway.
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PMID:Luteinizing hormone-releasing hormone induces nuclear factor kappaB-activation and inhibits apoptosis in ovarian cancer cells. 1106 44


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