Environmental quality and safety. Supplement最新文献

More than 40 plant species have been shown to contain substances that are active in biological assays for estrogenic activity. Such substances may be constitutive metabolic products of a plant, or be formed adaptively in response to environmental factors, such as fungal attack (e.g. coumestrol synthesis in alfalfa infected with Pseudopeziza medicagensis); in other instances estrogens may arise from microbial attack on plant material during storage (e.g. zearalenone formation from corn by Fusarium spp.) Phyto-estrogens may reach man through direct consumption of fresh fruit, vegetables and processed plant products (e.g. administration of olive or cornoil can induce vaginal keratinization in post-menopausal women); or---more relevant to this Symposium---by consumption of carcasses and products from animals fed estrogen-containing forage. Important pasture and forage plants shown to contain phyto-oestrogens include Trifolium subterraneum L, notably the cultivars Dwalganup, Mt. Barker, Yarloop and Marrar, T. pratense (red clover), T. fragiferum L. (strawberry clover), T. alexandrinum (berseem clover), Medicago sativa (alfalfa or lucerne) and Soya hispida (soya beans). A beneficial anabolic action of the estrogens contained in these plants has been implied, but not unequivically established. More attention has been paid to their noxious effects on livestock. On affected T. subterraneum pasture, castrated male sheep showed lactation, squamous metaplasia of the bulbo-urethral glands and urethral stenosis; infertility, variously attributed to suppression of gonadotrophin release and ovulation; faulty ovum transport; premature regression of corpora lutea; irreversible cystic hyperplasia of endometrial glands on prolonged exposure; dystocia and prolapse of the uterus. Sporadic incidence of phyto-estrogen induced infertility in cattle has been reported, attended by ovarian cyst formation. Estrogenic activity in forage plants has been reported from Australia, New Zealand, India, Sweden, Great Britain, Germany, Denmark, Holland, Finland, Egypt and Israel. The clover constituents chiefly incriminated for these effects are glycosides of the isoflavone derivatives genistein and its 4'-methyl ether biochanin-A, daidzein and its 4'-methyl ether formononetin, and pratensein; coumestrol and its 3'- and 4'-methyl ethers account for the estrogenic activity of alfalfa. The isoflavone content of subterranean clover may reach 3 percent of its dry weight, and the coumestrol content of lucerne may exceed 100 mug/g. Coumestrol and genistein compete with 17beta-estradiol for binding sites on the uterine cytoplasmic receptor and induce macromolecular synthesis in the uterus, but fail to induce ovum implantation in ovariectomized, gestagen-maintained rats. Uterotrophic activity of coumestrol and genistein given parenterally to sheep is approximately 10(-3) and 10(-5) times that of stilboestrol, respectively. Biological activity of ingested phytoestrogens is modified by r

A variety of anabolic agents are currently added to animal feeds to increase growth rate and improve feed efficiency. These compounds and their metabolites are largely excreted. Prior to the use of anabolic agents as feed additives and the advent of confined livestock production, natural recycling occurred which generally resulted in benefit to the animal with no known adverse effects on consumer health. However, the current interest in the use of animal excreta in livestock feed and the possible presence of anabolic agents and their metabolites from this practice has created an additional need for information on the occurrence of anabolic agent residues in consumer products. This report will consider the definition of anabolic agents in its broadest sense and discuss the research on hormones used in animal feed that may be found in animal excreta. In addition to feed additive residues, endogenous compounds may also be found in animal excreta. Endogenous estrogens and androgens have been detected in excreta from domestic livestock and poultry. Research results suggest that substantial estrogenic and androgenic activity may be detected in fresh animal excreta. However, little is known about the effects of various processing methods of excreta such as heat drying and fermentation on its hormonal activity. The effects of feed additive residues and endogenous hormones in excreta used for feed will be discussed relative to their impact on animal health and occurrence in animal products.

This paper will discuss data obtained on the growth promoting effects of metabolically active agents for avian species generally used for food production. The compounds to be considered are those with estrogenic, androgenic, or thyroid hormone activity. Estrogens have been studied most extensively with poultry. At physiologically active levels, estrogens markedly stimulate food intake and at times, weight gain. There is a marked increase in fattening in chickens fed estrogenic compounds and generally a decrease in nitrogen retention. There seems to be a particular stimulation of lipogenesis of estrogenic compounds to the extent that protein synthesis is depressed. Generally high levels of estrogenic compounds are required for metabolic effects. Estrogens have marked effects on circulating nutrient levels and also decrease the choline requirement of growing chicks. Thyroid active substances have been extensively studied. Iodinated casein has been shown to stimulate early growth especially in growing ducks. Efficiency of feed utilization is depressed by feeding iodinated casein and body fat content is reduced. Feathering may be improved by thyroid hormone and in species where feathers are economically imported, it is sometimes advantageous to use these compounds. Methyltestosterone has been shown to be growth stimulating for female chickens and turkeys but relatively ineffective for males. In general, androgens seem to be somewhat less effective in stimulating growth rate and nitrogen retention in domestic birds compared to effects observed in mammals. The role of growth hormone as an anabolic agent in birds is somewhat obscure. Mammalian growth hormone preparations seem ineffective in poultry. The anabolic agents that will be considered in this paper are the hormone active substances with estrogenic, androgenic, or thyroid activity. These will be considered primarily as they affect growth and carcass composition of various species of poultry and not in their normal physiological roles. When considering the role of these compounds in production of human food through their effects on animals, the effects on growth rate, feed efficiency, and carcass composition are primary traits of concern and many other interesting aspects of the physiological effects of these compounds cannot be considered. The paper will not be an exhaustive review of the literature but will attempt to document the effects of these agents on the productive characteristics of poultry.

In the use of anabolic agents, the most pronounced effect on growth is caused by estrogens. For this reason primarily attention will be given to the methods of detection of estrogen administration to fattening animals. The detection methods can mainly be divided in histological, biological, chemical, and immunological determinations and these will be briefly discussed in the light of the present situation in many countries, where the use of anabolic agents is prohibited. From the point of view of control, this prohibition is much easier to handle than a situation in which the application of some specified products is permitted. The possibilities and limitations of control, when certain anabolic agents are permitted for use, will be discussed and evaluated. The conclusion is drawn that in this latter case a sufficient control is very difficult if at all possible considering the methods of control available at the time.

As skeletal muscle is more developed in the male than in the female, it is supposed that androgens might be responsible for myotrophic or anabolic action. In this respect, many studies were made to try to answer the question: are androgens (or some of their metabolites) responsible for myotrophic action and by what mechanism? Do they act directly on skeletal muscle as on other target organs, or have they an indirect action on muscle, perhaps through a secondary stimulant (for instance synthesized in the liver)? Evidence is now presented that, in the rat's skeletal muscle, androgens likely act through the binding to a cytosoluble receptor, as they do in the ventral prostate. This receptor has analogous properties to all other androgen receptors. It is a proteinaceous (pronase sensible) "8S" component binding testosterone and androstanolone with high affinity and small capacity; it does not bind androstanediols. This finding and the increased incorporation of 3H-thymidine in nuclei and increased protein synthesis obtained in muscle cell culture after action of testosterone favour the concept that muscular cells are direct targets of androgens in skeletal muscles. Presently, the steroid specificity of receptor binding cannot be assessed quantitatively with crude cytosol preparation. While in ventral prostate, androstanolone has a higher affinity, the binding experiments have not yet indicated in muscle if the higher affinity of testosterone is related to differential binding of the two steroids, or to the complex effects of enzymes present in the extracts. In fact, evidence was obtained for 5alpha-reductase and 3alpha,beta-hydroxysteroid reductase activities under the same experimental conditions as for binding determinations. Therefore, the apparent antrostanolone binding in muscle could be lowered by transformation into androstanediols not binding to receptor, or the increase of apparent testosterone binding due to transformation into androstanolone. So the problem of whether testosterone or androstanolone or another natural steroid is the most effective myotrophic hormone in rat skeletal muscle remains unsolved. However, this animal model allows the study of certain interesting aspects of action of androgens on muscle. When receptor preparations are partially purified and not contaminated by metabolizing enzymes, different natural or synthetic steroids can be tested as to their affinity and anabolic effectiveness in muscle. It would be of pharmacological interest if receptor diversity made it possible to distinguish myotrophic action from virilizing activities. This in vitro system allows studying the mechanism of action of molecules which could have in vivo an anti-androgen effect and it is remarkable that radioactive testosterone and androstanolone can compete for receptor binding by an excess of estradiol, progesterone and cyproterone acetate...

The principal types of hormonal agents used in the production of meat for human consumption are estrogens, progestagens, and androgens. Only the last class is truly anabolic. Each type of compound named above has fairly characteristic toxic effects after prolonged intake. In this review, an attempt will be made to relate available information from experience with the administration of these three types of hormones to humans to the question whether sufficient amounts of these chemicals can remain in meat cut from carcasses of animals administered hormones during finishing to have deletarious effects on human ingesters. Present indications are that administration of stilbestrol to pregnant women may result in a somewhat increased incidence of cervical and vaginal cancers in their daughters; such administration appears to have no effect on the incidence of cancers in sons and only slight, if any, effect on that in the mothers. Other estrogens seem to have no specific effects on the incidence of cancer. Progestagens also are not known to induce any specific lesions. Although many androgens are known to produce edema, fever, and jaundice, they have not been found to cause specific lesions to any significant extent. With reference to stilbestrol, the doses given to the mothers of affected children have ranged between 5 and 125 mg/day. Because muscle, liver, and kidney from steers treated with stilbestrol in the usual way (s. c. implantation of a pellet at the base of an ear) have been found to contain less than 0.5 ppb of stilbestrol one month after implantation of the pellet, it is obvious that, to approach even the lowest clinically used dose of stilbestrol, a person would have to eat daily a quantity of such animal products that would be impossible to ingest. The findings that a mean of 26.4% of an oral dose of stilbestrol is excreted within 24 hours and that 99.5% is excreted within a week indicate that cumulation of this chemical within the body from the low level of intake provided by meats is not likely to reach a significant level. This would be so even though the animal product contained more than the 0.5 ppb mentioned above.

This presentation is limited to the three groups of steroid sex hormones which alone or in combination have been shown to be anabolic when used in farm animals. It seems essential for realistic evaluation of public health aspects of use of these hormones that the discussions include naturally occurring levels of the hormones. The following topics will be dealt with for each group of hormones: 1. Types and sources; 2. Production rates; 3. Plasma levels; 4. Tissue concentrations; 5. Metabolism and excretion. Gestagens. Progesterone and 20-dihydroprogesterones are mainly produced in ovaries and placenta. Production rates are estimated to 10 and 14 mg/24 hrs in pregnant goats and sheep, respectively. Plasma levels during the luteal phase are of the order of 2--10 ng/ml, during pregnancy somewhat higher. Muscular tissue from calves contain 0.25 mg/g. In dairy cows progesterone is excreted with the milk which contains up to 30 ng/ml; butterfat up to 300 mg/g. In ruminants progesterone is metabolized mainly to androgens excreted with faeces. In pigs large parts are metabolized to pregnanediols excreted with urine. Androgens. Testosterone is mainly secreted by testes. Boar testes also produce large amounts of dehydroepiandrosterone and its sulphate. Production rates have been estimated to be 10 mg and 40--50 mg/24 hrs. in boars and bulls respectively. Plasma levels in bulls and rams are generally 2--10 ng/ml, in boars 2--25 ng/ml. Adipose tissue levels up to 22 ng/g are reported for bulls. In ruminants epitestosterone seems to be a major metabolite excreted mainly with faeces. In boars, urinary 11-deoxy-17-ketosteroids are major metabolites of testicular dehydroepiandrosterone. Castration shows elimination to be rapid. Estrogens. 17beta-Estradiol and estrone are produced in ovaries and placenta and, in large amounts, in boar and stallion testes. Production rates in late pregnancy are estimated to 10 mg oestrone/24 hrs. in goats, 2 mg estrone and up to 28 mg 17beta-estradiol/24 hrs. in sheep. In cows much higher values are found. Boars and stallions produce huge amounts daily. Plasma levels in non-pregnant animals are at the pg/ml level. In late pregnancy levels of 2--4 thousand pg/ml are encountered in sows and cows, in sheep and goats lower levels. Calf muscular tissue contains up to 410 and 610 pg/g of estrone and 17beta-estradiol respectively. In muscle from pregnant heifers corresponding values were 120 and 860 pg/g in the 4th month and 2100 and 370 pg/g in the 9th month of pregnancy. Ruminants in large measure metabolize 17 beta-estradiol and estrone to 17alpha-estradiol which possesses low estrogenic activity. In pigs estrone dominates in blood and urine. Major routes of elimination arre with faeces in ruminants, with urine in pigs and horses. Elimination rates are high. Results obtained during the last few years clearly show that all three groups of steroid sex hormones occur in considerable concentrations in plasma and tissue...

Thirty castrated crossbreed lambs of 4 months age were divided into three groups. DES pellets (6 mg) were implanted subcutaneously in lambs of groups II and III, respectively at 4 and 7 months of age whereas those in group I served as controls. The lambs were fed on a dry fattening ration during a period of 29 weeks after which two lambs of each group were slaughtered and three lambs were also used in nitrogen balance studies. The body gains of lambs implanted with DES at 4 months of age were the highest. The growth promoting effect of the hormone in these lambs was significant during a period of 13 weeks after the implantation. The dietary nitrogen retained by treated lamb was significantly higher. The dressing percentage and weights of wholesale cuts in lambs implanted with DES were similar to those of control lambs. However, the percentage of meat in the lambs treated at 4 months of age was the highest. The protein and moisture contents of the tenth rib of these lambs were greater and the fat contents were lower than in the control animals. No DES residual activity was ever noted in the livers of slaughtered lambs. Effect of DES Implantation on Body Components. Six 2 year old Egyptian rams were used in a 2-month experiment, the duration being divided into three successive intervals. The 1st period served as a control. At the beginning of the 2nd period, DES was implanted subcutaneously. Total body water was measured using tritiated water, total muscle mass was determined by the creatinine excretion during 24 hrs, lean body mass, body rat, and nitrogen balance, were measured during the last 5 days of each experimental period. DES implantation increased the body weight of the ram by 10.4% and caused no significant change in total body water, body ash, or total muscle mass. However, body fat increased significantly. The efficiency of nitrogen utilization also increased significantly although nitrogen intake did not change. The maximum effects of DES were observed at the end of the second experimental period. Effect of Some Estrogens on Rumen Metabolism. Three DES treated and three untreated cross bred Egyptian rams were used for studying the effect of DES on rumen microorganisms. Ruminal activity, judged by the diurnal concentrations of volatile fatty acids (VFA) and ammonia-N determined 3 and 6 weeks after DES implantation, was greater in treated animals. When rumen contents from fistulated sheep were incubated in vitro with stilbestrol dipropionate (SDP), DES, and Estradiol dipropionate (EDP), a significant increase in the number and size of rumen ciliate protozoa was observed. The extent of increase varied according to the type and concentrations of added hormones and type of rumen protozoa. Further in vitro experiments indicated that the addition of DES, SDP, and EDP promoted the fermentation of starch by washed suspensions of mixed populations of ciliate protozoa. EDP seemed to show the greatest effect in stimulating VFA production by

The conversion of feed protein into body protein in growing pigs is rather unfavourable. With Dutch Landrace pigs only 30--40 percent of the digestible crude protein is converted into body protein. To study the influence of implanting 20 mg 17beta-estradiol + 140 mg trenbolone acetate per animal on this conversion ratio, three nitrogen-balance experiments were performed with castrated male pigs of 55--75 kg liveweight. In experiment 3 the energy balance was also measured. N-retention was significantly improved by the treatment. In none of the experiments the digestibility of the ration was influenced. With the pigs implanted at around 55 kg live weight, N-deposition during the period from 6--9 till 26--32 days after treatment was increased by on an average respectively of 24 percent (experiment 1), 60 percent (experiment 2) and 56 percent (experiment 3) as compared with a placebo. Where pigs of 75 kg were implanted, N-deposition was increased over the period from 2 till 28 days after implantation by 39 percent as compared with a placebo. In experiment 3 it was shown that the conversion of the metabolizable energy of the ration into energy deposited in the body (= protein + fat) was not considerably altered at 13--17 days after the treatment of pigs (weighing 55 kg) with anabolic agents. As compared with the placebo, N-deposition was increased by 40 percent and fat deposition was descreased by 15--20 percent. So the implantation with the anabolic agents has resulted in shift to a higher protein deposition and a lower fat deposition. The results of the balance determinations were confirmed in a comparative growth experiment, in which 14 castrated male Large Wht& x Landrace pigs of 56 kg weight (i.e. 69 days before slaughter at 90 kg live weight) were implanted with the aforementioned combination; 14 animals served as control. In the period from treatment till slaughter live weight gain was significantly improved by 6.5 kg; feed conversion was 0.3 units significantly lower than the control. Carcass weight was significantly higher for the treated group (difference compared with control 4.5 kg). Carcass quality was also improved; the carcasses of the treated pigs were longer and the thickness of the backfat was less. In a second comparative experiment on growth of castrated male pigs from 66 to 100 kg, the effect of the oral application of the combination ethinylestradiol (0.6 ppm, 1.2 ppm, and 2 ppm respectively in the feed) and trenbolone acetate (2 ppm in the feed) was studied. The three experimental groups and the control group consisted of 15 animals each. Live weight gain was significantly improved in the two groups with the higher levels of ethinyl estradiol (i.e. 4.4 kg and 6.9 kg respectively), feed conversion was significantly lower in all three anabolic agroups (i.e. 0.2, 0.3 and 0.4 respectively). Backfat thickness was less in all three anabolic groups and the carcasses were longer in the two higher dosage groups compared with the co

Sexual steroids are involved not only in the triggering of sexual activity but also in sex-linked social behaviour (aggressiveness etc.) The use of anabolic agents (particularly steroids) raises the problem of their possible interference with these mechanisms. In the normal male, an injection of androgen does not alter the level of sexual activity, which seems to be determined by nervous mechanisms. On the contrary, by feed-back in the hypothalamo-hypophysial mechanisms it exerts a depressive effect on the endogenous secretion. Female hormones have an inhibiting effect which works both by reducing the actual secretion of androgen and by direct action at two levels: the nervous receptors and the target organs of the genital apparatus. In the female, injections of exogenous hormones may interfere with the mechanisms regulating the oestrous cycle, e.g. inhibition of oestrous and of ovulation by progestagens, and luteotrophic or luteolytic action in the case of the estrogens. In an ovariectomized female the injection of testosterone propionate causes the appearance of sexual receptivity. The behaviour induced in this way is completely normal and free from any abnormal male component. The importance of this action has led to the presumption of a role played by the androgens in the normal triggering off of female sexual behaviour. It therefore seems that the nervous system of the female, but not of the male, possesses a potential bisexuality. The rate at which the hormone passes into the circulation appears to be more important than the actual type of hormone (estrogen or androgen) in causing the appearance in the female of sexual behaviour of one or the other sex. It has been suggested that estrogens might be the active steroid form necessary at the nervous structure level for initiating sexual behaviour in the two sexes, while the androgens would have to undergo aromatization in order to acquire their effectiveness at that level. Aggressiveness depends on the sexual hormones; the androgens are normally responsible for the high level of aggressiveness in males. On the other hand, in some species the characteristic aggressiveness of the female is explained by the presence of progesterone (e.g. hamsters). The territorial marking typical of the male of, for example, the dog, cat and rabbit species etc. is also due to the androgens. The pheromones usually depend on the sexual hormones (pheromones of sexual attraction which promote or inhibit aggression, etc.) A "sexualization" of the nervous system exists---e.g. of the hypothalamus---which is refelcted not only in the modes of hypophysial secretion but also in the type of sexual behaviour. This sexualization occurs through the loss of the possibility of a female-type reaction that occurs in the male under the influence of the androgenic secretions of the foetal or neonatal testicle. Therefore this action appears at an early stage and is conclusive...