It was reported in a previous study that serum estradiol-17β (E2) was elevated in rats after retrochiasmatic transection (FC). Serum E2 was also higher in estradiol cypionate treated, ovariectomized (ovx) rats that had been subjected to FC than in those that had not. This suggested that increased secretion of E2 was not the only factor responsible for elevated serum E2 after FC. To ascertain the contribution of decreased metabolism of E2 to this response, liver tissue slices were incubated with 3H-estradiol-17β, and the rates of 3h uptake and conversion to water-soluble conjugates were measured.The rate of uptake of 3H by the tissue was not indicative of the rate of conjugate formation. Livers of rats with high serum E2 exhibited lower rates of 3h uptake than those of rats with low serum E2. Even so, the formation of 3H conjugates was greater in liver of rats with high serum E2. As hypothesized, livers of rats with FC formed conjugates at a significantly lower rate than those of similarly treated rats without FC. Thus, FC of an intact rat leads to an increase in serum E2 by increasing the secretion of E2, and apparently also by decreasing the rate of E2 metabolism by the liver. 相似文献
Recently we have found that chemotactic factors stimulate neutrophils in suspension to aggregate. Because of an obvious analogy to platelet aggregation, we examined the influence of three prostaglandins on this process. Prostaglandins E1, E2 and F2α alone did not cause aggregation of the neutrophils but were able to partially inhibit the aggregation response induced by the synthetic chemotactic tripeptide, formly-methionyl-leucyl-phenylalanine. The minimal inhibitory concentrations for prostaglandins E1, E2 and F2α were 10−7, 10−6 and 10−5M, respectively. These results are similar to those found for the prostaglandin-induced inhibition of platelet aggregation. It may be, therefore, that neutrophil aggregation, like platelet aggregation, is modulated by intracellular prostaglandins and other products of arachidonic acid metabolism. 相似文献
We investigated some effects of prostaglandin E1 on the metabolism of rat parathyroid glands using a culture system containing basal Eagle's medium supplemented with 5–10% heat-inactivated rat serum. Rat parathyroid glands incorporate [3H]fucose and 14C-labeled amino acids into cellular glycoproteins and secrete some of these into the culture medium. Gel filtration chromatography separates these glycoproteins into three classes, the smallest of which (peak 3) is secreted with immunoreactive parathyroid hormone. In cultures of 48 h, prostaglandin E1 (1 μg/ml) specifically inhibits the secretion of peak 3 and of parathyroid hormone but has no effect on the incorporation of [3H]-fucose, 14C-labeled amino acids, or [3H]uridine into parathyroid glands. Cytochalasin B inhibits the secretion of parathyroid hormone and the incroporation of isotopic fucose and amino acids. Cortisol stimulates incorporation of [3H]fucose and the secretion of parathyroid hormone even in the presence of inhibitory doses of prostaglandin E1. It is concluded that, in organ culture, prostaglandin E1 inhibits the secretion of parathyroid hormone and of a specific glycoprotein the function of which may be related to the secretion of the hormone. 相似文献
The metabolism of i.v. estriol was investigated in two intact baboons and four with biliary fistulas. Urine and bile samples were collected periodically and the radioactivity extracted by Amberlite-XAD resin. Metabolites were separated and purified by a combination of DEAE-Sephadex chromatography, celite partition, specific enzyme hydrolysis of the conjugates and identification of the aglycones. The excretion and metabolism of estriol in the animals closely resembled those of the human. Intact animals excreted an average of 50% of the radioactivity in the urine during 12 hours and two animals with biliary drainage excreted an average of 40% in the urine and 49% in the bile. When the steroid was injected into the portal vein an average of 11.5% and 84% were excreted in the urine and bile, respectively.In the urine of intact animals, approximately 65.8% of the radioactivity was in the form of E3-16G; 14.2% as E3-3G; 13.4% as E3-3S and 5.1% as E3-3S-16G. Over 73% of biliary radioactivity from the peripheral injections was made up of E3-3S-16G and 3.6% as E3-16G and 8.3% as 3-sulfate. In the urine,however, 57% of the label was made up of E3-16G. No radioactive E3-3G was detected in the bile of any of the animals. Following simultaneous injection of 3H-E3 peripherally and 14C-E3 intraportally, the 3-glucosiduronate excreted in the urine was derived exclusively from the 3H-label. Based on the results obtained, the baboon has been shown to metabolize estriol in the same fashion as the human, with E3-3S-16G as the predominant biliary metabolite and E3-16G as the major urinary metabolite. As in the human, evidence was also found for an enterohepatic circulation of e3 in the baboon, 16-glucuronidation in the kidney, and extrahepatic (enteric?) formation of E3-3G. incubation of the baboon liver yielded 94% of the total conjugate as E3-16G without any trace of E3-3G. 相似文献
The dose-dependent effects of 9 prostanoids (PGA1, PGA2, PGE1, PGE2, PGF1α, PGF2α, PGD2, PGI2, 6 keto- PGF1α) on metabolism of cultured bovine articular chrondrocytes were investigated. Most prostanoids dose-dependently inhibited 35SO4= and 3H-glycine incorporation. At 25 μg/ml, the inhibitory sequence was A2D2>E2 = E1 = A1>6 keto-F1α>F1>F2, but sensivity (lowest dose eliciting inhibition) followed the sequence E2 > 6 keto-F1α = F1 > A2 = D2>E1>A1. At 25 μg/ml PGA2 also inhibited incorporation of 3H-cytidine and #H-thymidine, but had no significant effect on 3H-glucose or 14C-xylose incorporation. The inhibitory effect of PGA2 was apparent after 30 minutes exposure for 35SO4= and after 60 minutesd for 3H-cytidine, and was still present up to 72 hours following incubation in fresh non-PG-containing medium. PGI2 had no significant effect of 35SO4= incorporation but at concentrations below 10 μg/ml enhanced uptake of 3H-glycine.The PG-induced inhibitory effect was apparently not due to cell damage as indicated by measurement of 3H-glucose metabolism and lactate production. 相似文献
The relative potencies of the prostaglandins A1, A2, E1, E2, F2α and their 15-keto-, 15-keto-13,14-dihydro-, and 13,14-dihydro-metabolites were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2. All the prostaglandins (except PGF2α and its 15-keto-metabolites) relaxed the tissue. However, only PGE1, E2, and their 13,14-dihydro-metabolites, were effective at concentrations below 10−8 M. Therefore, events that alter metabolism of circulating PGs in the perinatal period may have significant effects on the relative patency or closure of the ductus arteriosus. 相似文献
The metabolism of 3H-estrone sulfate (3H-E1S) in 4 pregnant sheep, two injected i.v. and two i.m., has been studied. Intravenously injected 3H-E1S had a plasma half-life of approximately 8 min, and metabolic clearance rate of approximately 800 ml/min. Using this clearance rate and the previously published mean plasma concentration of E1S, the estimated production rate of E1S is between 8.8 nmol (3.3 μg) and 78.2 nmol (29.1 μg) per min from 2-day to 0-day before parturition.Intramuscularly injected 3H-E1S disappeared from plasma linearly and was completely cleared well within 3 hours. In all cases, whether i.v. or i.m. injected, the main metabolite isolated was 3H-estradiol-17β-3-sulfate, with only a trace amount as 3H-estradiol-17β-3-sulfate. 相似文献
We have previously demonstrated that decreased cortical prostaglandin metabolism can contribute significantly to an increase in renal tissue levels and activity of prostaglandin E2 in bilateral ureteral obstruction, a model of acute renal failure. In the present study, we have further investigated whether alterations in prostaglandin metabolism can occur in a nephrotoxic model of acute renal failure. Prostaglandin synthesis, prostaglandin E2 metabolism (measured as both prostaglandin E2-9-ketoreductase and prostaglandin E2-15-hydroxydehydrogenase activity), and tissue concentration of prostaglandin E2 were determined in rabbit kidneys following an intravenous administration of uranyl nitrate (5 mg/kg). No changes in the rates of cortical microsomal prostaglandin E2 and prostaglandin F2α synthesis were noted at the end of 1 and 3 days, while medullary synthesis of prostaglandin E2 fell by 47% after 1 day and 43% after 3 days. Cortical cytosolic prostaglandin E2-9-ketoreductase activity was found to be decreased by 36% and 76% after 1 and 3 days respectively. No significant changes were noted in cortical cytosolic prostaglandin E2-15-hydroxydehydrogenase activity after 3 days. Cortical tissue levels of prostaglandin E2 increased by 500% at the end of 3 days. These data demonstrate that in nephrotoxic acute renal failure, decreased prostaglandin metabolism (i.e., prostaglandin E2-9-ketoreductase activity) can result in increased tissue levels of prostaglandin E2 in the absence of increased prostaglandin synthesis and suggest that alterations in prostaglandin metabolism may be an important regulator of prostaglandin activity in acute renal failure. 相似文献
The metabolism of 3H-androstenedione (Δ4 -A) and 3H-estriol (E3) was studied in 12 human breast tumors. Part of each tumor was analyzed for estrogen receptor content. Aliquots of tumor homogenates were incubated for 2 hr separately with 3H-δ4-A and 3H-E3 in the presence of appropriate cofactors. No distinct differences emerged in the profiles of the unconjugated metabolites of 3H-δ4-A, the major compounds in the approximate order of descendence being androsterone, androstanedione, testosterone, 5α-androstane-3α,17β-diol, epiandrosterone, and dihydrotestosterone. One tumor homogenate from an infiltrating lobular carcinoma converted 3H-Δ4-A to glucosiduronate metabolites (11%), of which androsterone, 6.4%; testosterone, 1.6%; and androstanediol, 0.6% predominated. The homogenate of this tumor and two other tumors converted 3H-E3 to 3H-E3-3S. Conversions of E3 to E3-3S In the other tumor homogenates were less than 0.6%. No correlation between receptor content and the capability of the tumor to conjugate Δ4-A or E3 evolved. However, correlations between steroid hormone metabolism and tumor histopathology may exist. 相似文献
It is well known that the metabolic clearance rate (MCR) of a hormone is Influenced highly by the level of its specific binding protein. It was interesting, therefore, to study the metabolism of estradiol-17β (E2) in an animal model such as the rabbit where there is a lack for a highly specific binding protein for the steroid. The kinetics of the hormone was studied in relation to the thyroid state, namely in rabbits receiving thyroxin or propylthiouracil.In the absence of any significant decrease of the level of the rabbit androgen binding protein (R-ABP), the accelerated MCRE2 and the elevated conversion ratio of estradiol to estrone (CR E2→E1) observed in hyperthyroid rabbits were attributed to the important role of metabolizing enzymes in the liver and/or extrahepatic tissues. In hypothyroid rabbits, while the CR E2→E1 decreased significantly the MCRE2 was not altered. 相似文献
La3+ was found to inhibit the secretion of 5-hydroxytryptamine and the production of thromboxane B2 by washed platelets exposed to collagen or thrombin. In addition, La3+ inhibited secretion in response to sodium arachidonate, although the conversion of arachidonate to thromboxane B2 was not affected.La3+ was also found to enhance the accumulation of cyclic AMP under basal conditions and in response to prostaglandin E1, in washed platelets. The inhibition of cyclic AMP accumulation by ADP was prevented by La3+, suggesting that the effect of ADP on cyclic AMP metabolism was dependent upon the presence or flux of calcium at the platelet membrane.La3+ inhibited the activity of adenylate cyclase in platelet lysates both in response to prostaglandin E1 and to F?, indicating a possible effect at the catalytic subunit of the enzyme. None of the observed effects of La3+ could be reversed by the addition of Ca2+ up to 10 mM. The stimulation of cyclic AMP production by La3+ may largely explain the inhibitory effect of La3+ upon platelet secretion and thromboxane B2 production. These results also suggest that Ca2+ localised at the platelet plasma membrane may be important in the regulation of cyclic AMP metabolism. 相似文献
Semliki Forest virus was grown in BHK cells and labeled in vivo with radio-active monosaccharides. promnase digenst of the virus chromatographer on Bio-Gel P 6 revealed glycopeptides of A-type and B-type. (For the nomenclature see Johnson J. and Clamp J.R. (1971) Biochem. J. 123, 739–745) The former was labeled with [3H]fucose, [3H]galactose, [3H]mannose and [14C]glucosamine, the latter only with [3H]mannose and [14C]glucosamine. The three envelope glycoproteins E1, E2 and E3 were isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subjected to pronase digestion. The glycoproteins E1 and E3 revealed glycopeptides of A-type. E2 revealed glycopeptides of B-type. E2 yielded additionally a glycopeptide (Mr3100) which was heavily labeled from [3H]galactose, but only marginally from [14C]glucosamine, [3H]fucose and [3H]mannose. Wether this glycopeptide belongs to the A-type or not remains uncertain. The apparent molecular weights of the A-type units measured by gel filtration were 3400 in E1 and 4000 in E3; the B-type unit of E2 had an apparent molecular weight of 2000. Combined with the findings of our earlier chemical analysis these data suggast that E1 and E3 contain on the average one A-type unit; E2 probably contains one 3100 dalton unit plus one or two B-type units. 相似文献
A single dose of tritiated estradiol-17β (3H-E2β) was injected i.v. into 5 high egg producing White Leghorn hens, 31 weeks of age, at 19.2 ± 2.1 (mean ± S.D.) hr before oviposition. Blood (2 ml) was sampled at approximately 5 min intervals over 40 min. Whenever possible, metabolites were monitored and identified by the double isotope technique with the addition of the corresponding 14C-labelled standards to plasma prior to analysis. The metabolic half-life and clearance rate of 3H-E2β in plasma were 10.9 ± 1.9 min and 118 ± 18 ml/min/kg body weight, respectively. The calculated production rate of E2β at 19.2 hr before oviposition was 19.5 ± 5.7 ng/min based on the plasma level (93±22 pg/ml) measured at that time. The relative concentrations (% of plasma radioactivity) of the major metabolites isolated at 5.7 ± 0.6 min post injection were, in descending order: estradiol-17β-3-sulfate (E2β-3S : 14.9 ± 2.7), estradiol-17α-3-sulfate (E2α-3S; 5.7 ± 0.3), estrone (E1; 4.6 ± 0.5), estrone sulfate (E1S; 2.2 ± 0.5), and estradiol-17 α (E2α; 1.2 ± 0.4). As time proceeded, the relative concentration of E2α-3S gradually increased so that by 43.2 ± 1.0 min it became the most abundant identifiable metabolite (12.3 ± 1.1) followed by E2β-3S (9.1 ± 1.7), E2S (1.2 ± 0.6), E1 (0.7 ± 0.4) and E2α (0.3 ± 0.2). These findings are consistent with the view that one of the major pathways of E2β metabolism in the circulation of the hen is via E2β E2β?3S ?E1S E2α-3S. 相似文献
Using both pulse injections and constant infusions of 3H-mestranol (3H-ME) (1) and 3H-ethinyl estradiol (3H-EE) we have studied the metabolism of these compounds in non-users and users of oral contraceptives. Following pulse injection of 3H-ME the disappearance of radioactivity could be described as a function which was the sum of two exponentials. Studied by both types of administration there was no difference in the metabolism of 3H-ME in the two groups; the overall mean ± SE metabolic clearance rate (MCR) was 690 ± 45 1/day/m2, the mean ratio of the concentrations of radioactivity as EE following administration of ME (CRBBM, E) was 0. 23 ± 0. 02 and the mean [ρ]BBM, E (fraction of administered ME measured in blood as EE) was 0. 19 (95% confidence limits = 0.15 – 0. 23).Following pulse injection of 3H-EE the disappearance of radioactivity was best described as a function which is the sum of three exponentials. Results from both types of administration revealed no difference in the metabolism of 3H-EE between non-users. The overall mean ± SE MCREE was 630 ± 30 I/day/m2. The MCREE is significantly (0. 02 > P > 0. 01) less than the mean MCR for estradiol reported previously, in both non-users and users of oral contraceptives. The use of oral contraceptives containing estrogens and progestins does not appear to influence the metabolism of the estrogen used. Approximately 20% of mestranol is converted to and appears in the blood as ethinyl estradiol. 相似文献
3 substances, B1, B2, and E1 were isolated from culture medium extracts ofAureobasidium pullulans by reversed phase liquid chromatography and subsequent liquid chromatographic purification steps on silica gel. The 3 compounds inhibited the metabolism ofSaccharomyces cerevisiae and showed toxic effects in the growth inhibition test toEscherichia coli andBacillus subtilis. Elementary analysis and mass spectroscopical methods revealed sum formulas of C23H22O6, C22H20O6 and C24H28O3 for B1 B2, and E1 and molecular weights of 394, 380, and 364, respectively. Mass spectroscopical, UV-, IR-,13C-NMR, and1H-NMR-spectroscopical investigations revealed polycyclic, non-aromatic compounds containing several carbonyl functions and double bonds and, most notably, spiroepoxy-functions, in the case of B1 and B2. 相似文献
Effects of prostaglandins (PGs) E1, E2, F2α and I2 in a wide range of concentration were examined in mesenteric and cerebral arteries isolated from mature baboons. PGs E1, E2 and F2α at low concentrations (10−10 to 10−7 M) elicited relaxation in helically cut strips of cerebral arteries precontracted with phenylephrine. In contrast, the PGs did not cause relaxation in the mesentric artery. PGI2 (10−9 to 10−6 M) produced marked relaxation in both arteries. The EC25 for PGI2 in the mesenteric artery was significantly lower than that in the cerebral artery. During baseline conditions, cerebral arteries contracted in response to high concentrations (greater than 10−7 M) of PGs E1, E2 and F2α. In mesentric arteries, a large contraction was induced by PGs F2α and E2 but not by PGE1. Arachidonic acid (10−6 M) produced an aspirin-inhibitable relaxation in both arteries to a similar extent, so that the vasodilator PG(s) formed in the two different arterial walls appear to exert a similar relaxant action. Thus, the baboon mesenteric artery was more sensitive to PGI2 for the relaxant effect than was the cerebral artery, while PGs F2α, E1 and E2 caused only a contraction in the mesenteric artery but both relaxation and contraction in the cerebral artery. 相似文献
Radioimmunoassays of platelet prostaglandins E1 and F1α in platelet rich plasma or platelet suspension, demonstrate that both PGE1 and PGF1α are present at higher concentrations than prostaglandins E2 and F2α. Gas chromatography — mass spectrometry determinations of prostaglandins E1 and E2 in resting washed platelets confirm this difference. Lastly, there is a greater incorporation of [1-14C] acetate into prostaglandins E1 and F1α compared to that into prostaglandins E2 and F2α. 相似文献
The uptake, metabolism and subcellular distribution of oestradiol and oestriol in endometrial, myometrial and vaginal tissue of postmenopausal women under physiological conditions were studied by giving 3H-labelled oestradiol or oestriol in subphysiological doses by continuous infusion lasting 12 h before hysterectomy. The three tissues obtained from each woman were separated into three fractions: two cytosol fractions (free oestrogens and specifically bound) and one nuclear fraction. The results show an accumulation of both oestrogens in the target tissues, we found an approximately 33 times higher [3H]E2 concentration in endometrium (dpm per g) than in plasma (dpm/ml), 20 times in myometrium and 10 times in vaginal tissue. After the E3 infusions the tissue/plasma gradient was 37 for endometrium, 19 for myometrium and 11 for vagina. In plasma and tissues a metabolite of E3 could tentatively be identified as 16α-hydroxyoestrone. The subcellular distribution showed that 60–80% of E2 and E3 is accumulated in the nuclear fraction of all tissues studied, no nuclear bound oestrone could be detected. From these results the conclusion was drawn that oestradiol still is the major tissue oestrogen in postmenopausal women and that it is mainly nuclear bound. Endometrium of postmenopausal women accumulates higher concentrations of E2 and E3 than vaginal tissue from the same individual, no preferential uptake of oestriol occurs under physiological conditions. 相似文献