Effects Of Diethylstilbestrol Research Articles

The effect of quercetin, a widely distributed flavonoid in food and drink, on cytosolic aldehyde dehydrogenase: a comparison with the effect of diethylstilboestrol

Quercetin is a flavonoid found in red wine and many other dietary sources. Observations concerning the state of ionisation and the stability of the compound over a range of pH are presented. Quercetin is a potent inhibitor of cytosolic aldehyde dehydrogenase at physiological pH when the concentration of either the substrate or the cofactor is relatively low, but it has an activatory effect when the concentrations of substrate and cofactor are both high (1 mM). Gel filtration experiments show that quercetin binds very tightly to the enzyme under conditions where the compound is neutral and when it is ionised. The binding is less in the presence of NAD +. Quercetin cuts down the ability of the resorufin anion to bind to the enzyme. The observations are explained by a model in which quercetin binds competitively to both the coenzyme-binding site and the aldehyde-binding site; binding in the latter location, when the enzyme is in the form of the E-NADH complex, accounts for the activation. The effects of quercetin are significantly different in some respects from those of diethylstilboestrol; this is explained by the latter being able to bind to the aldehyde site but not the NAD + site. The possibility that quercetin may affect aldehyde dehydrogenase in vivo is discussed.

The effect of diethylstilboestrol on the in vitro growth of human ectocervical cells.

The effect of chronic exposure to diethylstilboestrol (DES) over the concentration range 10(-4)-10(-6) M on the in vitro growth of cells derived from the squamo -columnar junction of the human cervix has been examined. DES over the dose range 10(-4)-2 X 10(-5) M inhibits cervical epithelial cell (HCE) growth in terms of colony formation and colony expansion. This effect involves both an effect on cell proliferation, as measured by cell number and mitotic index, and an induction of differentiation as measured by an increase in the number of PAS positive cells (glycogen accumulating cells) and in the number of cells with cornified envelopes. At lower doses of DES, 10(-5)-5 X 10(-6) M, the efficiency of colony formation and colony size are not inhibited but mitotic index and cell number are decreased and the fraction of differentiating cells is increased. The effects of DES on HCE cell growth can be modified to some extent by epidermal growth factor (EGF). EGF at 10 ng/ml, increases the fraction of proliferating cells, induces cellular hypertrophy, reduces stratification and the fraction of differentiating cells in HCE colonies. DES, at all concentrations other than 10(-6) M, in the presence of EGF inhibits cell proliferation but does not prevent the EGF induced cellular hypertrophy, reduction in stratification or reduction in the fraction of differentiating cells.

Differential staining of chromosomes and spindle and its use as an assay for determining the effect of diethylstilboestrol on cultured mammalian cells

Differential staining of chromosomes and spindle and its use as an assay for determining the effect of diethylstilboestrol on cultured mammalian cells

Effect of diethylstilboestrol on phosphatidylcholine biosynthesis and choline metabolism in the liver of roosters.

It has been known for 40 years that oestrogens stimulate phospholipid metabolism in roosters. We have investigated in vivo the mechanism for this effect. Young roosters were injected daily with 1 mg of diethylstilboestrol for 1--3 days. At 4 h after the last injection, 30 microCi of [Me-3H]choline was injected into the portal vein. At periods up to 3 min the livers were freeze-clamped and choline and its metabolites were extracted and resolved by t.l.c. Hormone treatment in the first 2 days resulted in a 2-fold increase in phosphorylation of [Me-3H]choline and a decrease in the oxidation of [Me-3H]choline to [3H]betaine. The concentrations of phosphocholine in liver were increased 2-fold during the first 2 days concomitant with a 2-fold increase in the rate of phosphatidylcholine biosynthesis. After 3 days of hormone treatment, many of the above effects were reversed and the rate of phosphatidylcholine biosynthesis decreased to approx. 60% of the control value. The results suggest that the initial hormone treatments activate choline kinase within 4 h and, thereby, divert choline form oxidation to betaine. The resulting increased phosphocholine concentrations cause an increase in the activity of CTP:phosphocholine cytidylyltransferase, which results in a doubling of the rate of phosphatidylcholine biosynthesis. After 3 days of hormone treatment, the biosynthesis of phosphatidylcholine is decreased, most likely by an effect on the cytidylyltransferase reaction.

Effect of diethylstilboestrol on phosphatidylcholine biosynthesis in the liver of roosters.

Effect of diethylstilboestrol on phosphatidylcholine biosynthesis in the liver of roosters.

Time-Studies of the Changes in the Sex-Dependent Activities of Enzymes of Hepatic Steroid Metabolism in the Rat during Oestrogen Administration

This investigation was undertaken to elucidate the amount of oestradiol and duration of its administration necessary to cause complete feminization of the activities of cytoplasmic 3 alpha- and 17 beta-hydroxysteroid dehydrogenase, microsomal 3 alpha- and 3 beta-hydroxysteroid dehydrogenase and microsomal 5 alpha-reductase in male rat liver. With the exception of cytoplasmic 3 alpha-hydroxysteroid dehydrogenase, 5 microgram oestradiol/d for 8 days and less was sufficient to cause complete feminization. The order of oestrogen sensitivity was cytoplasmic 3 alpha-hydroxysteroid dehydrogenase greater than microsomal 3 beta-hydroxysteroid dehydrogenase greater than microsomal 3 alpha-hydroxysteroid dehydrogenase greater than microsomal 5 alpha-reductase greater than cytoplasmic 17 beta-hydroxysteroid dehydrogenase. Although the changes occurring after oestradiol administration are qualitatively the same as after testectomy, they occur more rapidly. This rules out the possibility that oestradiol exerts its effect via androgen deprivation. Diethylstilboestrol administration causes the same changes in cytoplasmic 17 beta- and microsomal 3 beta-hydroxysteroid dehydrogenase activity as oestradiol, although the dosage must be increased 100 fold. The effect of diethylstilboestrol on 5 alpha-reductase activity changes with the dose applied. Doses up to 100 microgram/d partially feminize the activity, but at higher doses the enzyme activity is repressed.

THE EFFECTS OF STILBOESTROL AND QUINESTROL UPON COAGULATION AND FIBRINOLYSIS DURING THE PUERPERIUM

The effects of stilbestrol and quinestrol on blood coagulation and f ibrinolysis were studied during the puerperium. Stilbestrol significant ly (p less than .05) increased Factors IX and X during the 1st week of the puerperium though levels returned to normal by the 6th week after delivery. Quinestrol significantly increased Factors II (p. less than .01) IX (p. less than .02) and X (p less than .05) during the 1st week of the puerperium. Factor II values remained significantly higher 6 weeks after delivery (p less than .01). During the 1st week of the puerperium plasma antithrombin levels were significantly lower in stilbestrol patients (p less than .02). Plasma antithrombin III levels were significantly lower in estrogen-treated patients 6 weeks after delivery (p less than .05). There were no marked increases in serum antithrombin III levels in any of the groups. Stilbestrol and quinestrol increased concentrations of plasminogen and antiplasmin during the 1st week of the puerperium. Quinestrol patients had significantly elevated levels of plasminogen and antiplasmin 6 weeks after delivery (p less than .01). The results suggest that the inhibition of lactation by estrogens may pose an increased thrombogenic risk.

Role of catecholamines in the mediation of peripheral effects of female sex hormones.

The effect of diethylstilboestrol (DES; 0.5 mg/100 g) and progesterone (2.5 mg/100 g) was studied on the catecholamine content of adrenals and uteri of seven day ovariectomized albino rats. The agents were administered i.p. on alternate days for one week and the tissue catecholamine content was determined spectrophotofluorometrically. DES treatment increased the total adrenaline contents of adrenals and uterus. On the other hand progesterone caused a decrease in the level of catecholamines in both the tissues. These findings are discussed in relation to the actions of female sex hormones on cardiovascular and genital systems.

Role of Catecholamines in the Mediation of Peripheral Effects of Female Sex Hormones

The effect of diethylstilboestrol (DES; 0.5mg/100g) and progesterone (2.5 mg/100 g) was studied on the catecholamine content of adrenals and uteri of seven day ovariectomized albino rats. The agents were administered i.p. on alternate days for one week and the tissue catecholamine content was determined spectrophoto-fluorometrically. DES treatment increased the total adrenaline contents of adrenals and uterus. On the other hand progesterone caused a decrease in the level of catecholamines in both the tissues. These findings are discussed in relation to the actions of female sex hormones on cardiovascular and genital systems.

A note on the effect of diethylstilboestrol on the performance of lambs

Two trials were undertaken to test the effect of different levels of diethylstilboestrol (DES) on the performance of Egyptian castrated male (wether), male (uncastrated) and female lambs. Ninety crossbred lambs in groups of 10, comprising 30 wethers, 30 male and 30 female lambs were used.

THE EFFECT OF TESTOSTERONE AND PROGESTERONE ON THE RESPONSE OF THE RETICULO-ENDOTHELIAL SYSTEM AND REPRODUCTIVE TRACT TO OESTROGEN IN THE MALE MOUSE

SUMMARY In intact and orchidectomized animals testosterone had no effect on the reticulo-endothelial system (RES) when administered alone; it potentiated the stimulant effect of 17β-oestradiol on the RES, but had no effect on the RE stimulation produced by diethylstilboestrol. Progesterone was a mild RE stimulant; it had no effect on the RE stimulation produced by 17β-oestradiol or diethylstilboestrol. Both testosterone and oestrogen caused weight increase in the levator ani of orchidectomized animals; progesterone had no effect. Testosterone and progesterone had no effect on the myotrophic action of 17β-oestradiol, but both compounds inhibited the myotrophic effect of diethylstilboestrol. The results show that in the male, as in the female, the action of oestrogen on the RES is independent of its action on the reproductive tract, although these two biological activities are contained in the same molecule.

Effect of diethylstilboestrol on adipose-tissue lipids

1. The effect of diethylstilboestrol on the fatty acid composition of adipose-tissue lipids of the ox (Bos taurus) was studied. 2. The capsula adiposa (perirenal) was shown to contain more total saturated fatty acids, whereas more total unsaturated fatty acids were found in the panniculus adiposus (subcutaneous). 3. Significantly more stearic acid and linolenic acid were obtained from the capsula adiposa, whereas the panniculus adiposus contained more myristoleic acid, palmitoleic acid and oleic acid. 4. Implanting diethylstilboestrol significantly increased the deposition of the saturated fatty acids, particularly stearic acid. 5. A decrease in the deposition of total unsaturated fatty acids, myristoleic acid, palmitoleic acid and linoleic acid can also be attributed to the diethylstilboestrol treatment.

Effects of Rat Strain, Stilbestrol and Testosterone on the Occurrence of Hemorrhagic Diathesis in Rats Fed a Ration Containing Irradiated Beef

Experiments were designed to investigate the difference between 2 strains of rats (Holtzman and Sprague-Dawley), and the effects of stilbestrol and testosterone on the ocurrence of hemorrhagic diathesis. The rats were fed ground beef exposed to 5.58 Mrad doses of Co/sup 60/ gamma radiation. Mortality was 58% for Sprague-Dawley rats, significantly higher than the 22% found for Holtzman rats. The average prothrombin rate, 50 for Sprague-Dawley rats at the end of the third week was significantly lower than 83 for Holtzman rats, prothrombin rates being expressed as 1000/sec. Sprague-Dawley rats were significantly less resistant to hemorrhigic disease than Holtzmann rats. Stilbestrol completely prevented hemorrhages and subsequent deaths, but testosterone increased both. The effect of testosterone was independent of growth. Stilbestrol decreased the prothrombin rates slightly and testosterone decreased them significantly. Stilbestrol decreased body weight gains, its effect being greater on Holtzman than on Sprague-Dawley rats. Testosterone increased growth in orchiectomized rats but had no effect on feed intake. Stilbestrol decreased the weight of seminal vesicles, prostates, and tests. Testosterone increased the weight of seminal vesicles and prostates but decreased the weight of testes. Stilbestrol was more potent than testosterone in inhibiting the secretion of hormones by the pituitary. Estrogen administrationmore » did not affect the prothrombin rate of rats fed a ration containing 2.79-Mrad irradiated beef, but increased it in those that received the 5.58-Mrad irradiated beef. It is suggested that estrogen overcame defective coagulation, but had no effect when the prothrombin rate was normal. (TCO)« less

Effects of stilbestrol on pituitary-adrenal function in male and female rats.

SummaryStilbestrol administration produced apparently similar increases in pituitary and adrenal weights and losses in body weight upon comparison of male and female rats. Pituitary ACTH content was more than doubled in females and unchanged in male animals. Pituitary RNA and DNA were both unchanged in males, whereas RNA (but not DNA) was increased in females. Adrenal RNA was increased in both sexes while DNA was unchanged in males and decreased in females. Plasma Cpd. B levels after stress or ACTH were unaffected in males and markedly reduced in females. Biological half-life of Cpd. B was shortened and hepatic metabolism of the steroid enhanced in treated males. Opposite changes were observed in female rats. Adrenal steroidogenesis in vitro was inhibited in female rats. An increment in steroidogenesis was demonstrated in males per total gland whereas a decrease obtained per unit gland weight. Male responses became similar to those in the female by administration of a more potent dose of stilbestrol.

Effects of Stilbestrol in Altering Carcass Composition and Feed Lot Performance of Beef Steers2

Effects of Stilbestrol in Altering Carcass Composition and Feed Lot Performance of Beef Steers2

Effects of Stilbestrol and a Combination of Progesterone and Estradiol on Growing-Finishing Swine

Forty-eight Poland China barrows were used in an experiment designed to study the influence of subcutaneous stilbestrol and progesterone-estradiol (high and low level) implants on average daily gain and carcass composition. The hormone implants had no significant effect on gain; although stilbestrol and the high level progesterone-estradiol combination (500 mg.–10 mg.) tended to reduce growth rate. The progesterone-estradiol implants decreased average backfat probe significantly. Carcasses of the control and treated barrows were similar; however, those from barrows implanted with the high level of progesterone and estradiol showed a trend toward increased leanness.

COMMITTEE ON NUTRITION

IMPLANTATION and feeding of various synthetic and natural estrogenic hormones especially diethylstilbestrol, to achieve improved efficiency of feed and better quality of carcass is a common practice among producers of livestock and poultry in this country. Androgenic agents have been used only experimentally to date. The preparations dosages and techniques employed are regulated by the Food and Drug Administration. Despite their requirement that no detectable residue of estrogenic hormones be present in edible tissues of treated animals offered for sale, some individuals maintain that the use of these hormones should be banned entirely because they believe that controls are inadequate to insure proper usage, and that analytic methods are not sensitive enough to detect minute quantities of hormones, whose repeated ingestion even in trace amounts might prove harmful. Fortunately, extensive data have been gathered on the physiologic effects of stilbestrol and other estrogenic agents, their therapeutic uses and toxicology. Also, the quantities of estrogenic residues in the tissues of treated animals have been determined. Greatest concern has been expressed over effects of stilbestrol on reproductive function on growth, and its possible carcinogenic properties. There is no doubt that stilbestrol can suppress ovulation in women if given in adequate amounts during the proper period of the menstrual cycle; and a relatively large dose (25 mg) may produce temporary impotence, but not sterility, in the male. These effects do not persist, however, when the dosage is discontinued, as the drug is destroyed and excreted in 3 or 4 days. Relatively little is known about the specific effects of stilbestrol on children since its therapeutic use has concentrated on adults.

The effect of diethylstilboestrol, hexoestrol and testosterone on the growth rate and carcass quality of fattening beef steers

The use of the hormones, diethylstilboestrol, hexoestrol and testosterone propionate, as growth stimulants in beef cattle has been studied.The subcutaneous implantation of 60 mg. stilboestrol into steers fattening in yards produced a highly significant increase in rate of gain (65%) and little difference in the yield and quality of the carcass. The implantation of 24 nig. or 36 mg. of diethylstilboestrol or 30 mg. hexoestrol into Friesian bullocks fattening on pasture produced highly significant increases in rates of gain (29%, 48% and 33% respectively). No significant difference was found in the rates of gain produced by these three treatments.The oral administration of 10 mg. diethylstilboestrol per head per day for 168 days or the oral administration of 20 mg. rising to 40 mg. testosterone propionate per head per day for 154 days to dizygotic twin steers on equal feed intake significantly increased rate of gain by 15% and 21% respectively Feed efficiency as measured by the pounds of feed required to produce a pound of gain was significantly improved by both treatments. Carcass yield and carcass quality were not significantly affected by either treatment. No significant differences were found between the two treatments.Examination of the thyroid and adrenal glands of treated and untreated steers revealed no consistent changes in size due to treatment. The gonadotrophin and thyrotrophin content of the anterior pituitary glands of treated and untreated cattle were compared using the male chick bioassay. The results showed that a lower gonadotrophin content was not a factor associated with the extra growth due to treatment, but in two out of three experiments there was some evidence that sex-hormone treatment leads to a mild hyper-thyroidism which, in turn, resulted in a decrease in the thyrotrophin content of the anterior pituitary gland. It was concluded that hyperactivity of the thyroid gland was probably more important in accounting for the extra growth than hyperactivity of the adrenal cortex.

Some Effects of Stilbestrol and Related Hormones on Feedlot Performance and Carcass Merit of Fed Lambs

Some Effects of Stilbestrol and Related Hormones on Feedlot Performance and Carcass Merit of Fed Lambs

Influence of a protein-free diet on the immediate and latent effects of stilbestrol.

The absence of protein from the diet of stilbestrol-treated rats modified, largely quantitatively the response to the hormone. Stilbestrol, per se, induced a body weight loss which was greater in the protein-depleted than in the protein-fed animal. Recovery on an adequate protein diet, after withdrawal of the hormone permitted an immediate recouping of body weight losses, whereas animals on the protein-deficient diet did not recover body weight losses. Stilbestrol administration increased excretion of nitrogen indirectly by restriction of food intake. This nitrogen loss was augmented by protein depletion. The marked retention of nitrogen by animals recovering on an adequate diet was more pronounced in the treated animal but rats continued on the protein-deficient diet maintained a negative nitrogen balance. The absence of protein from the diet diminished the anticatabolic influence of stilbestrol on total liver protein. Recovery on the basal diet allowed the repletion of liver protein but further decreases in liver protein concentration followed recovery on the deficient diet. A marked increase in the concentration of liver fat appeared concomitantly with the progressive depletion of liver protein in both treated and untreated groups.