Concentrations Of Diethylstilbestrol Research Articles

Surface modifications evoked by estradiol and diethylstilbestrol in isolated endometrial cells: evidence from lectin probes and extracellular release of lysosomal protease.

Endometrial cells were isolated from the uteri of ovariectomized rats. The inhibitory effect of alpha-methyl-D-mannoside on fluorescein-labeled concanavalin A (Con A) binding to these cells indicates that they possess specific binding sites for Con A. The lectin also mediates adsorption of homologous erythrocytes to these cells. Both Con A binding and Con A-mediated hemadsorption to endometrial cells are depressed at 4 C compared with these functions in cells maintained at 22 C. Gross elevations in lectin-mediated hemadsorption to endometrial cells are evident following prior exposure to 1 X 10(-9)M concentrations of diethylstilbestrol (DES) or estradiol-17beta, but not to the physiologically inactive 17 alpha-epimer, at 22 C. The enhancement of hemagglutinability cannot be attributed to a corresponding increase in lectin binding at 22 C. Although estrogen treatment elicited significant increments in Con A binding as early as 5 min after addition of estrogen to cell suspensions, the increment in agglutination attributable to hormone treatment consistently ranged from 1.5-3 times greater than the increase in lectin binding. These estrogenic effects were reduced by incubation of the endometrial cells at 4 C or when cortisol, 3 X 10(-6)M, was present with estradiol-17beta. In parallel experiments, treatment with DES and estradiol-17beta, but not estradiol-17 alpha, also enhanced the release of cathepsin B 1 and acid phosphatase from uterine segments into the particle-free extracellular media in which the tissues had been incubated for 30-60 min. The marked increment in the extracellular activity of the lysosomal hydrolases induced by estrogen treatment was suppressed in cells incubated at 4 C or when cortisol was present concomitantly. These and related data suggest the hypothesis that acute increments in lysosomal hydrolase activity may contribute to cell surface alterations which have been described in both normal and aberrant processes of cell growth.

The effect of altered hepatic function on the toxicity, plasma disappearance and biliary excretion of diethylstilbestrol

The present investigation was prompted by the observation that the toxicity of diethylstilbestrol (DES) was about 140 times greater in bile duct-ligated (BDL) rats than in control rats when dimethylsulfoxide was the vehicle (24-hr LD50: 0.75 vs 100 mg/kg, respectively). The DES was also more toxic (about 70 times) in the BDL rats when ethyl alcohol was the solvent (0.47 vs 34 mg/kg), and was 5 times more toxic in the BDL rats when administered in propylene glycol (100 vs 530 mg/kg). Since it appeared that altered hepatic function markedly alters the acute toxicity of DES, the plasma disappearance and biliary excretion of DES (0.118 mg/kg, iv) were measured in control rats and in rats with altered hepatic function (produced by surgical removal of two-thirds of the liver, ip injection of 1 ml CCl 4/kg, or bile duct ligation). All three procedures of altering hepatic function decreased the plasma disappearance of DES. In the BDL rats, the total plasma concentration of DES did not decrease over the 2-hr period, suggesting that even when the biliary route of excretion is blocked, other routes are not efficent for the excretion of DES. During the furst 15 min after DES administration, the biliary excretory rate of DES was 2.1 μg/min/kg in control rats and 1.2 μg/min/kg in the rats that had a 2 3 hepatectomy or CCl 4. Therefore, impaired hepatic function increased the plasma concentration and toxicity of DES as it decreased its conjugation and biliary excretion.

Action of diethylstilbestrol on staphylococci: further observations on the effect of resting cells.

Diethylstilbestrol (DS) has been shown to be active against staphylococci and other gram-positive bacteria but not against gram-negative microorganisms. The present study extends these findings. Standardized suspensions of (14)C-labeled Staphylococcus aureus serotypes III and IV and Shigella flexneri were prepared and exposed to pharmacological concentrations of DS (1 to 20 mug/ml) under diverse environmental conditions; the cells were removed by membrane filtration and the presence of radioactive substances in release to the supernatant fraction was followed by standard radioisotopic techniques. Controls were exposed similarly to the hormone vehicle alone (buffer containing 2% ethyl alcohol). DS at bactericidal concentrations above 6 mug/ml caused significant leakage of cellular radioactivity of S. aureus labeled with (14)C-glucose and (14)C-glutamic acid within 1 to 4 hr after exposure to DS. Maximum leakage of radioactivity occurred under anaerobic conditions at 37 C. Absorption studies of (14)C-labeled DS indicated that the affinity of S. flexneri for DS is markedly less than that of S. aureus. This might be one reason for the resistance of gram-negative bacteria to DS.

Action of Diethylstilbestrol on Staphylococci: Further Observations on the Effect of Resting Cells

Diethylstilbestrol (DS) has been shown to be active against staphylococci and other gram-positive bacteria but not against gram-negative microorganisms. The present study extends these findings. Standardized suspensions of (14)C-labeled Staphylococcus aureus serotypes III and IV and Shigella flexneri were prepared and exposed to pharmacological concentrations of DS (1 to 20 mug/ml) under diverse environmental conditions; the cells were removed by membrane filtration and the presence of radioactive substances in release to the supernatant fraction was followed by standard radioisotopic techniques. Controls were exposed similarly to the hormone vehicle alone (buffer containing 2% ethyl alcohol). DS at bactericidal concentrations above 6 mug/ml caused significant leakage of cellular radioactivity of S. aureus labeled with (14)C-glucose and (14)C-glutamic acid within 1 to 4 hr after exposure to DS. Maximum leakage of radioactivity occurred under anaerobic conditions at 37 C. Absorption studies of (14)C-labeled DS indicated that the affinity of S. flexneri for DS is markedly less than that of S. aureus. This might be one reason for the resistance of gram-negative bacteria to DS.

Diethylstilbestrol effect on the in vitro synthesis of progesterone in the bovine corpus luteum.

The ability of diethylstilbestrol to influence the synthesis of progesterone in the bovine corpus luteum was investigated. Slices of tissue were incubated with several concentrations of diethylstilbestrol and an exogenous TPNH source. No exogenous precursors of progesteione were added. At concentrations greater than 0.01 μM, diethylstilbestrol inhibited progesterone synthesis up to 37% when TPN plus glucose-6-phosphate was used as the TPNH source. Diethylstilbestrol did not inhibit progesterone synthesis when TPNH or isocitric acid plus TPN was used in place of TPN and glucose-6-phosphate. Analysis for 20-hydroxypregn- 4-en-3-one, androst-4-ene-3,17-dione, testosterone, estradiol and estrone showed that the decrease in progesterone content was not a result of increased metabolism to any of these products. These results indicated that physiologically significant concentrations of diethylstilbestrol are capable of decreasing progesterone synthesis by inhibiting bovine corpus luteum glucose-6-phosphate dehyd...

エストロゼンおよびゴイトロゼン投与が反芻動物の第1胃内微生物の数および活性に及ぼす影響

The authors wanted to study on the mechanism of the effects of estrogen or/and goitrogen in cattle fattening from the points of digestion physiology.The effects of these two hormonal substances on numbers and activities of rumen micro-organisms were examined in vivo and in vitro. Diethyl-stilbestrol (DES) was used as an estrogen and methylthiouracil (MTU) as a goitrogen.The effects of DES or/and MTU on the numbers of rumen micro-organisms in sheep were examined twice in vivo with different basal rations but no significant effect was found. The effects of these two hormonal substances on ratios of kinds of rumen protozoa in sheep were examined but no significant result was found either. It was found that when the concentrates and alfalfa pellet were given to the sheep, the number of rumen protozoa increased, and the ratio of Entodinium also increased but the one of Diplodinium decreased, comparing with sheep when the concentrates and hay were given.Using artificial rumen, the effects of DES or/and MTU on performance of cellulose digestion of rumen bacteria in cattle were examined in vitro. But no significant effect was found when the concentration of the hormonal substances was the same with the one which had been used ordinarily for cattle fattening. When the concentration of DES in tube of artificial rumen was over 5mcg/ml, the performance of cellulose digestion of rumen bacteria decreased.Using the artificial rumen, the effects of DES or/and MTU on performance of volatile fatty acids production of rumen protozoa in cattle were examined in vitro but no significant effect was found.From the results mentioned above, the authors guessed that the principal mechanism of the actions of hormonal substances in cattle fattening was not in the part of digestion physiology but in the other part, for example, the part of endocrinology.

Inhibition of a microbial glucose-6-phosphate dehydrogenase by diethylstilbestrol.

Diethylstilbestrol readily inhibits the reduction of triphosphopyridine nucleotide by a glucose-6-phosphate dehydrogenase prepared from fractionated cell-free extracts of Aerobacter aerogenes. Hexestrol and dienestrol exert a similar influence but the dehydrogenase system was not sensitive to a number of steroids. The degree and extent of inhibition was a function of the diethylstilbestrol concentration. The inhibition could not be reversed by the addition of excess glucose-6-phosphate or triphosphopyridine nucleotide but the suppression could be relieved by the addition of increments of the fractionated extract containing the glucose-6-phosphate dehydrogenase enzyme. Several other enzymes such as isocitrate, alcohol, and malate dehydrogenases were found to be present in the same fraction but reduction of nucleotides by these enzymes was not influenced by the steroids or synthetic estrogen. A tentative hypothesis is that diethylstilbestrol may interact directly with certain enzymes, under specified experimental conditions, thereby regulating the rate of the enzymatic reaction. These findings thus suggest yet another mechanism whereby a synthetic estrogen may regulate intermediary metabolism.

The effects of various estrogens and steroid substances of sex differentiation in the fowl.

An account is given of the effects of the immersion of 4108 fertile, preincubation, hen‘s eggs into ethanol solutions of diethylstilbestrol (DES), and of 1524 such eggs into isopropyl alcohol solutions of DES. The percentage of hatched genetic male chicks showing feminization at hatching increased, on the average, with increasing concentrations of DES in the dipping solutions and, up to a point, with increased immersion time. Occasional small percentages of genetic females were virilized by the ethanol solutions, but were not seen in the experiments were isopropyl alcohol was the solvent. Maximal morphological reversions were observed in isopropyl alcohol solutions of DES. Ethinyl estradiol in ethanol solution also induced significant percentages of feminization, while testosterone in ethanol irregularly induced limited masculinization. Allopregnan-21–ol–3,20-dione acetate either in ethanol or in isopropyl alcohol reduced the percentage of eggs hatching and tended to be differentially lethal to female embryos.

Effects of Diethylstilbestrol on Allium cepa

Observations are reported on seeds, bulbs, and roots of onion which had been treated with concentrations of diethylstilbestrol ranging from 66 γ to 100 mg. in 10 cc. of tap water. Contrary to findings of Lettre (2, 3) on animal tissue in vitro, no confirmation of a colchicinelike action on mitosis was obtained in the absence of toxic effects. This is in agreement with the work of Ludford and Dmochowski (4) on mouse tumors. A nonspecific auxin-like response was obtained on the bulbs in the form of an overgrowth of the bulb base, similar to overgrowths on bulbs infected with Bacterium tumefaciens (1).