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)

Changes in four hydrolytic enzymes, namely acid phosphatase, alkaline phosphatase, arylsulphatase A and B, of the cervix of the rat and hamster have been studied during the 4-day oestrous cycle. All four enzymes showed maximal activity on the day of oestrus and least activity on day 2 of dioestrus. All the enzymes showed significant reduction of activity after ovariectomy, arylsulphatase A and B showing the earliest changes in specific activity. A single subcutaneous injection of 0-02 microng oestradiol-17beta/rat increased the especific activity of arylsulphatase A and B from the low ovariectomized level to that observed in control oestrous animals within 18 and 6 h respectively. A higher concentration of oestradiol 17beta (2-0 microng) had an inhibitory effect. Progesterone was without effect on arylsulphatase B activity, but when given (2-0 mg) with 0-02 microng oestradiol-17beta, it inhibited the response to oestrogen. Cycloheximide prevented the rise in arylsulphatase B activity occurring after oestrogen injection, suggesting a regulation of cervical arylsulphatase B at the level of protein biosynthesis. These results suggest that arylsulphatase B activity may be induced by oestrogen in the cervix of the rat.
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PMID:Enzymic changes in the cervix of the rat and hamster during the oestrous cycle and the effect of steroids. 1 40

Cells of sarcoma 180 and of Ehrlich's carcinoma were maintained by serial transplantation in male and female Swiss mice. Either estrogen, progesterone, or testosterone were injected im at doses of 1 mg/mouse. Ascitic fluid was aspirated at intervals of 1, 3, 6, 24, and 48 hours following hormone injections. Enzyme activities were analyzed by subjective grading according to the intensity of staining reaction. Estrogen produced enhancement of alkaline phosphatase activity in both types of cells in both sexes of mice. Progesterone produced increased alkaline phosphatase activity in both types of cells from female hosts but an inhibitory effect in male hosts' cells. Testosterone produced no change in enzyme activity in tumor cells of female hosts but in male hosts it inhibited enzyme activity of sarcoma 180 cells and activated activity in carcinoma cells. The effect of all 3 hormones on acid phosphatase activity was activation. With adenosine triphosphatase, estrogen stimulated the activity in both types of tumor in both sexes. Progesterone stimulated cells from male hosts with little or no effect on cells from female hosts. This enzyme was resistant to testosterone. Succinate dehydrogenase activity under similar conditions was different. Estrogen reduced this activity and progesterone produced some inhibition of activity. Testosterone inhibited the sarcoma cells but had no effect on carcinoma cells of either sex. Others have shown that sex hormones affect the enzyme activities beyond the target tissues, particularly in the liver, kidney, and pancreas. Different responses of the enzymes seemed to depend on the endogenous hormonal status of the mice.
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PMID:Enzymatic responses of transplanted tumour cells towards estrogen, progesterone and testosterone. 13 8

The refractory period that follows the period of sensitivity to a decidual stimulus in ovariectomized hormone treated mice was investigated. Medroxyprogesterone acetate provided constant progestin concentrations and silastic implants containing oestradiol maintained constant nidatory oestrogen concentrations. The nidatory stimulus was provided by crushing the uterus with a haemostat or by the intrauterine instillation of arachis oil. The decidual response was assessed by measuring changes in uterine weight or by examining the stroma for the presence of alkaline phosphatase. Sensitivity to the oil was first observed approximately 14 h after the insertion of the oestradiol implant but this sensitivity had waned by 32 h and was absent at 40 h. Crushing the uterus initiated a decidual response in mice treated with progestin alone but if the oestradiol implant was inserted then the uterus was responsive to crushing 24 h after insertion but not at 45 h. The traumatic decidual cell reaction (crushing), although not requiring nidatory oestradiol for its successful initiation, was nevertheless subject to the refractoriness that followed oestradiol sensitivity.
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PMID:Timing of the window of uterine sensitivity to decidual stimuli in mice. 129 31

Progesterone (P)-induced PRL secretion in estradiol (E)-primed monkeys is not due to direct pituitary stimulation, because lactotropes do not express progestin receptors (PR). However, the hypothalamus, particularly the tuberoinfundibular dopaminergic system (TIDA), plays a major role in the regulation of PRL secretion. To determine whether hypothalamic dopamine neurons are progestin target cells, the colocalization of PR and tyrosine hydroxylase (TH), a phenotypic marker of dopaminergic neurons, was examined with double immunocytochemistry. Two methods for visualizing the antigens were applied; the first was a dual peroxidase method, and the second was a peroxidase-alkaline phosphatase method. In addition, the question of whether E induces PR in dopamine neurons was explored. Spayed female monkeys were treated with empty Silastic capsules, E-filled capsules for a period of 28 days, or E capsules supplemented with P capsules for the last 14 days of E treatment. Only the E- plus P-treated monkeys exhibited an increase in serum PRL during the P treatment period. Frontal sections at the level of the optic chiasm and arcuate nucleus were examined for the colocalization of TH and PR. After E treatment, hypothalamic PR-positive cells increased in both intensity and number. Neurons expressing both TH and PR were detected in the rostral hypothalamus, lateral to the third ventricle (A11-rostral) and in a discrete subventricular population (A11-subvent). The lateral population continued caudally (A11-caudal). The A11-subvent population exhibited little steroid regulation. Of the remaining A11 TH neurons, approximately 20% exhibited PR in the spayed and E-treated groups. Addition of P doubled the percentage of PR-containing TH neurons in this group. Although very few TH-positive neurons in the ventral arcuate nucleus contained PR (A12-ventral), many double labeled neurons were observed in the dorsal arcuate region (A12-dorsal). Ventral arcuate TIDA neurons were not regulated by steroids, but E plus P increased PR expression in A12-dorsal. Double labeled cells were rarely seen in the zona incerta (A13) or the emerging ventral tegmental area (A10). In summary, P probably does not act directly on ventral arcuate TIDA neurons to stimulate PRL secretion. However, the frequency of PR-positive dopamine neurons in the A11-rostral, A11-caudal, and A12-dorsal groups increased with E and P treatment. Therefore, the contribution of the PR-positive periventricular dopamine neurons to progestin-stimulated PRL secretion may be important.
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PMID:Immunocytochemical colocalization of hypothalamic progestin receptors and tyrosine hydroxylase in steroid-treated monkeys. 135 39

Progesterone, which is normally produced in the endoplasmic reticulum, was found to be rapidly degraded in the cytosolic fraction of the guinea pig adrenal cortex in vitro. Assuming this finding reflects what happens in vivo raises a question as to the source of progesterone for interacting with a nuclear progesterone-binding protein (P4-BP) that exists in this model system. It was subsequently found that pregnenolone, which in contrast to progesterone is relatively stable in the cytosol, was converted to progesterone by endogenous nuclear 3 beta-ol dehydrogenase. It was also determined that the nuclear-derived progesterone specifically bound to the nuclear P4-BP which is distinct from the classical progesterone receptor. The guinea pig adrenocortical cytosol contains a specific pregnenolone-binding protein (P5-BP) that could be virtue of its pregnenolone binding activity regulate the conversion of pregnenolone to progesterone in the nuclear compartment and thereby reduce the binding of progesterone to the nuclear P4-BP. A partially purified P5-BP preparation markedly inhibited the nuclear conversion of pregnenolone to progesterone and reduced the binding of progesterone to the nuclear P4-BP (P5-BP did not directly inhibit binding of progesterone to the nuclear P4-BP). The ability of P5-BP to inhibit the conversion of pregnenolone to progesterone was destroyed by heat and alkaline phosphatase treatment. The binding of pregnenolone to the P5-BP, as previously reported, is regulated by phosphorylation/dephosphorylation, and alkaline phosphatase-treated P5-BP loses the ability to bind pregnenolone; this process can be reversed by a cytosolic kinase. This provides a mechanism for controlled release of bound steroid. These results suggest that P5-BP regulates the nuclear conversion of pregnenolone to progesterone and thus the binding of progesterone to the nuclear P4-BP.
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PMID:The nuclear conversion of pregnenolone to progesterone and subsequent binding to the nuclear progesterone-binding protein in the guinea pig adrenal cortex: a possible regulatory role for the pregnenolone-binding protein. 169 80

Long-acting medroxyprogesterone acetate (MPA) effect on some important parameters of calcium metabolism in patients with glucocorticoid-induced osteoporosis (GCO) was evaluated. Twelve steroid-dependent asthmatic male patients with GCO were administered 200 mg of MPA (Depo-Provera) intramuscularly, and had fasting serum samples obtained at baseline and at weekly intervals for 5 consecutive weeks. Baseline serum samples were also obtained from 12 control healthy male subjects matched for age. The following measurements were made from each serum sample: osteocalcin (OC), skeletal (SAP) and total alkaline phosphatase (TAP), calcitonin (C), insulin-like growth factor I (IGF1), 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Significantly lower baseline serum levels of OC and C were found in the patients with GCO than in controls (P less than 0.001). Following MPA administration in GCO patients statistically significant and sustained increases in OC, SAP and C were noticed during the next 5 weeks. No significant differences in baseline levels for TAP, IGF1, 1,25(OH)2D and 25(OH)D between GCO patients and controls were found, and no significant changes following MPA administration in GCO patients were obtained for these parameters. In conclusion, when administered to patients with GCO, MPA seems to stimulate the osteoblastic activity as suggested by sustained increases in OC and SAP serum levels, and also enhances the C production by the C-cells of the thyroid.
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PMID:Effects of medroxyprogesterone acetate on some parameters of calcium metabolism in patients with glucocorticoid-induced osteoporosis. 182 84

Testis of male albino rats treated with depot medroxyprogesterone acetate DMPA, at the dose of 1 mg/animal/day for 60 days showed degenerative changes in the late spermatids. The changes were related with the mitochondrial sheath of the midpiece, including the plasma membrane enclosing the mitochondria and the mitochondrial cristae. Except lactate dehydrogenase and alkaline phosphatase, all the testicular marker enzymes, viz. beta-glucuronidase, hyaluronidase, sorbitol dehydrogenase and acid phosphatase registered a significant decrease. The ultrastructural and biochemical changes are correlated, as the cellular degeneration is responsible for decrease in the activity of the marker enzymes.
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PMID:Effect of depot medroxyprogesterone acetate on testis of albino rats: ultrastructural and biochemical studies. 183 39

Seventy-three healthy, postmenopausal women, aged 45-54 years, were randomly assigned to one of three groups for 2 years of treatment: 17 beta-oestradiol 1.5 mg on days 1-12 and 17 beta-oestradiol 1.5 mg + desogestrel 150 micrograms on days 13-24 (E2/DG) or oestradiol valerate 2 mg on days 1-11 and oestradiol valerate 2 mg + medroxyprogesterone acetate 10 mg on days 12-21 (E2V/MPA) or placebo. Fifty-seven women (78%) completed the study. Bone mineral content of the distal regions of the forearms (measured by single photon absorptiometry, SPA) and bone mineral density of the spine (measured by dual energy X-ray absorptiometry, DXA) showed increases of 0.5-1% and 4-5%, respectively, in the hormone groups over 2 years. The placebo group exhibited a decrease in spinal bone density of 2% per year, and in the forearm of 2.5-3.5% per year. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium) decreased significantly to premenopausal levels in the hormone groups but remained unchanged in the placebo group. In both hormone groups total cholesterol decreased by about 9% (P less than 0.001), whereas low density lipoprotein cholesterol decreased by 16% in the E2/DG group and 20% in the E2V/MPA group (P less than 0.001). High density lipoprotein cholesterol showed only minor, insignificant changes in the hormone groups. The placebo group had virtually unchanged values. Climacteric symptoms, including hot flushes, were significantly reduced in both hormone groups. Bleeding occurred regularly in about 80% of the women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Desogestrel in hormone replacement therapy: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding. 183 79

A mathematical model of pressure/flow relationships in straight and tortuous intracerebral arterioles is presented. Using this model, it is predicted that patients with severe tortuosity would never be able to tolerate an appreciable decrease in MAP. This morphological alteration may explain the inability of a few hypertensive and normotensive elderly patients to tolerate periods of mild reductions in blood pressure. The alkaline phosphatase histochemical staining technique is potentially an excellent method of establishing the identity of deep white matter signal alterations seen on MRI because of its ability to trace the vascular supply from the brain surface to the lesion.
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PMID:Does tortuosity in cerebral arterioles impair down-autoregulation in hypertensives and elderly normotensives? A hypothesis and computer model. 200 99

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.
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PMID:Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate. 214 9


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