[Protein anabolic agents. Development of the concept of the anabolic agent. Comparative study of anabolic agents most currently used].
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Anabolic Agents↗
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Scientific report on anabolic agents in animal production. Scientific Working Group on Anabolic Agents.
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Anabolic Agents↗
Metabolism of endogenous and exogenous anabolic agents in cattle.
The endogenous anabolic agents, estradiol-17 beta, progesterone and testosterone are steroids that are quickly metabolized by the liver and are not very active when administered orally. Estradiol-17 beta is excreted by the bovine in bile as free estradiol-17 alpha, and by swine, in urine, as glucuronides and sulfates. In ruminants, the primary metabolite of progesterone is pregnandiol and that of testosterone is epitestosterone. In horses, the metabolites of these compounds are primarily 17 ketosteroids. Esters of the endogenous anabolic agents are rapidly hydrolyzed and the nonesterified forms follow the same biotransformation pathways as the natural compounds biosynthesized by the animal. The exogenous anabolic agents, such as trenbolone acetate, zeranol and diethylstilbestrol, may be active by the oral route and are less readily metabolized in the liver than the endogenous anabolics. Their metabolic pathways may be complex and lead to excreted forms after glucuronide conjugation. With respect to biochemical mechanism of action, it can be assumed that the anabolics act like all steroids by way of intracellular receptors. Biotransformations could lead to more reactive molecules that may bind themselves to normal constituents of the organism. Bound metabolites are generally formed later than free metabolites, and are considered less toxic with a lower level of bioavailability.
Anabolic Agents↗
The absorption, distribution and excretion of anabolic agents.
The metabolic fate of the anabolic agents, diethylstilbestrol, hexestrol, trenbolone acetate, zeranol and the endogenous steroids are discussed under the headings absorption, distribution and excretion. There is an optimum concentration of anabolic agent in the systemic circulation that results in a maximum increase in growth rate of farm animals. This optimum blood concentration should be maintained over a long period. However, there is rapid metabolism and excretion of anabolic agents with short half-lives in blood, and metabolic clearance rate equals entry rate. The rate of absorption of the agent, which is determined by formulation and site of administration, is most important and is best achieved by the use of slow release implants. The pattern of exponential absorption from compressed pellets of single anabolic agents is not ideal, and a more constant payout of drug, in particular estradiol-17 beta, is best achieved in combined preparations of agents or from silicone rubber implants impregnated with the agent. The high metabolic clearance rate and rapid excretion of anabolic substances influences the distribution of residues. Outside the site of administration, less than 1% of the administered dose is present in the animal. The lowest concentrations of residues are found in muscle and fat, higher concentrations are present in liver and kidney and the highest concentrations are in the bile, urine and feces.
Anabolic Agents↗
Recycling and degradation of anabolic agents in animal excreta.
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.
Anabolic Agents↗
9 clinical cases of nonhealing pressure ulcers in patients with spinal cord injury treated with an anabolic agent: a therapeutic trial.
Anabolic steroid agents may potentially promote wound healing in individuals with spinal cord injury who have long-standing wounds. Nine patients hospitalized on the Spinal Cord Injury Service of the VA Medical Center, Bronx, NY, received treatment with an anabolic agent and amino acid supplement. Selection of patients was based on having at least 1 of the following criteria: (1) nonhealing pressure ulcer of at least 2 months' duration with no change or worsening status, and/or (2) full-thickness pressure ulcer through fascia into muscle, tendon, or bone. Previous and current pressure ulcer histories were determined by review of the hospital records when available and/or self-reporting by the patient. Eight of 9 patients had nonhealing wounds of 2 months' to 5 years' duration. One patient was included because of having a large, full-thickness pressure ulcer of reportedly 2 weeks' duration. Except for 1 Stage III pressure ulcer, all others had Stage IV pressure ulcers.Three patients had documented weight loss (>10% of total body weight), 3 had no recent weight loss, and 3 refused to be weighed. Patients were treated from 1 to 12 months with oxandrolone (20 mg/day) and glutamine (20 g/day). Eight of 9 patients completely healed: 3 after 3 months, 2 after 4 months, 1 after 6 months, and 2 after 12 months of treatment. One patient was discharged against medical advice after 1 month of treatment with a healing wound and was lost to follow-up. Although clinical case studies have limited usefulness for determining effectiveness of drug therapy on wound healing, these initial observations of successful treatment with an anabolic agent and amino acid supplement have been encouraging.
Adult↗
Anabolic agents: adjuncts to nutrition support.
Anabolic agents as adjuncts to nutrition support therapy have been used to improve malnutrition and establish anabolism. Growth hormone, insulin-like growth factor, and anabolic steroids have been studied for their potential to reverse the catabolic process and promote anabolism. This paper reviews several anabolic agents and their possible role in nutrition support therapy.
Journal Article↗
Pharmacological and endocrinological studies on anabolic agents.
When used in connection with animal production the term "anabolic agents" covers a wide range. Ther steroidal male and female sex hormones are included in this list, as are the nonsteroidal estrogens. For the clinician and for the endocrinologist, anabolics are only steroids chemically related to testosterone and 19-nortestosterone. Estrogens, though possessing anabolic properties, too, do not belong to this class. This paper will deal with anabolic agents in in the stricter sense of which mainly trenbolone acetate combined with hexestrol has been recommended for bull and heifer fattening. To consider possible consumer injury from ingestion of meat from anabolic agent treated animals, it is necessary to know the pharmacological properties of the agents, the doses producing certain effects or might produce, and the levels of residues in the meat. Trenbolone acetate will be compared with the following anabolic agents: methenolone acetate, methandrostenolone, nandrone, androstanazole, and 19-nortestosterone. The activity spectrum of trenbolone acetate is similar to that of 19-nortestosterone or those anabolics that are derived from 19-nortestosterone. The compound has about three times stronger androgenic effect than testosterone propionate. Its index of dissociation between anabolic/androgenic activity is 2--3. This index is 3--10 for the other anabolic agents. As regards the virilizing potency, trenbolone acetate is also on the top of the list. It seems that androgenicity and degree of virilization run paralle. The antigonadotropic activity (inhibition of ovulation and testicular growth) of trenbolone acetate exceeds that of testosterone propionate by the factor 3. The compound is not estrogenic and seemingly not or only weakly progestationally active. In principle, the androgenic activity (symptoms of virilization) as well as the antigonadotropic effect (disturbances of the menstrual cycle in women, inhibition of spermiogenesis in men) of trenbolone acetate might be noted. This risk, however, can be excluded by mere calculation. In rats, 0.1 mg/kg trenbolone acetate have an antigonadotropic effect. This corresponds to a daily dose of 5--7 mg in humans. By the same extrapolation, a daily human dose of 100 mg can be calculated for androgenic activity. Such factors of conversion are, of course, not precise because rats are much less sensitive to androgens and anabolics than humans. Thus, testosterone propionate is active only in daily doses of 10--20 mg. If in humans trenbolone acetate also has three times the activity of testosterone propionate, effects in man had to be counted with not less than a daily intake of 3--5 mg trenbolone acetate. The dose which is recommended for livestock fattening is 300 mg. IT can, therefore, be excluded almost with certainty that the meat would contain such large amounts of hormone residues.
Anabolic Agents↗
Human safety considerations from the use of anabolic agents in foodproducing animals.
The various anabolic agents used in food-producing animals may differ in terms of toxicological considerations related to evaluating human safety. Aside from initial toxicological testing, after chemical characterization of the compound to be administered and its related metabolites expected to occur as residues in food, most synthetic anabolic agents are subjected to chronic/carcinogenicity testing because of usage pattern likely to lead to the occurrence of residues in derived edible products. Initial testing requirements include acute and subchronic studies in appropriate rodent species including a reproduction test with the first generation offspring tested for 90 days post-weaning. This subchronic study serves to indicate potential problems with reproductive performance, foetal toxicity, birth deformities, and other chronic or preneoplastic conditions. The Food and Drug Administration (FDA) may grant approval for certain usages of specific compounds using a 2.000-fold safety margin in relation to a "no deleterious effect" level from the subchronic studies, with upper residue limits of 0.1 ppm in tissue and 0.01 ppm in milk or eggs if there are no indications that further testing should be required. If higher residue limits are requested, the petitioner must perform lifetime testing in two rodent species including in utero exposure and a minimum of three dose levels. Other rodent offspring should be carried for a total of three generations. A six to twelve month study in a non-rodent population is required. Teratology studies might be rquired in at least two species. If no carcinogenic potential is observed, a 100-fold safety margin in relation to the no effect level is generally accepted as the safe exposure level for residues. Should a statistically significant increase in tumors be observed in the test animals as compared to controls, the compound will be classified as a carcinogen or a suspect carcinogen depending on histopathological observations...
Anabolic Agents↗
The effectiveness of anabolic agents in increasing rate of growth in farm animals; report on experiments in cattle.
In many countries anabolic agents are successfully used to increase the rate of growth of cattle. In the past widespread use was made of cheap synthetic estrogens such as diethylstilbestrol and hexestrol. However, new legislation in certain countries has restricted the use of synthetic estrogens. This has resulted in an intensive search by industry for alternative agents. On the one hand natural steroid hormones like estradiol, testosterone and progesterone were studied, while on the other hand products like an active compound of the resorcyclic acid lactones and the synthetic anabolic steroid trenbolone acetate were developed. Administration of anabolic agents to cattle is done in three ways. (1) The agent may be fed orally by incorporation into the concentrate feed or as a simple additive top dressing. If the agent is metabolised in the rumen, oral administration may still be possible by using coated materials which avoid rumen metabolism with subsequent absorption of the steroid from the small intestine. (2) The agent may be administered as a slow release implant, e.g. trenbolone acetate or various combined preparations of an androgen and estrogen. (3) Administration by repeated injection. This latter method is often impractical. Anabolic agents are normally administered to beef cattle or culled dairy cows during the last few months of the finishing period. Maximum weight gain performance in different types of cattle requires selection of the correct anabolic agent. Increased performance in female cattle is better when an androgenic steroid is administered. However, in intact males (bulls) best performance is only obtained when an estrogen, alone or in combination with an androgen, is administered. Castrate animals (steers) do best if a smaller amount of estrogen is combined with an androgen and administered, however there is evidence that androgen alone is as effective. In summary therefore, an additional response in growth of cattle may require the presence of an estrogen, as endogenous estrogen in the female and the exogenous form in the male. Only when this condition is met will administration of androgenic anabolic steroids result in maximum benefit, often improving the effect of estrogen given on its own. Anabolic agents have some beneficial effect on appetite. They may not affect the digestive processes of the alimentary system. They have a positive effect on nitrogen retention. The liver almost certainly has a central role in the regulation of nitrogen retention. Recent experiments suggest that urea entry rates in ruminants may be lowered, thus making available more nitrogen for protein synthesis. Muscle protein synthesis is altered with changes in carcass conformation. There are some changes in fat redistribution. How all these processes are integrated is not yet known. The possibility that anabolic agents establish a new hormonal status which is favourable to growth will be discussed...
Anabolic Agents↗
Metabolic fate of anabolic agents in treated animals and residue levels in their meat.
Anabolic agents applied in animal production can be classified as sex hormones, as far as one aspect of their biological activity is concerned. In respect to their chemical nature the agents can be divided into three sub-groups: (a) steroids natural to the body (endogenous steroids); (b) steroids foreign to the body; (c) other compounds foreign to the body. After exogenous application (oral or parenteral) metabolism of compounds in group (a), e.g. 17beta-estradiol or testosterone, follows the pathways for the identical endogenous hormones; i.e. enzymatic transformation of the biologically active molecule into less active compounds. Excretion seems to occur predominantly via the feces, followed by the excretion via the urine. Steroids foreign to the body (group [b]) may be simple esters of endogenous steroids (estradiol benzoate, testosterone propionate) or compounds with basically modified steroidal structures, like trenbolone acetate (estra-4, 9, 11-trien-17beta-OH-3one-Ac). After enzymatic cleavage of an ester in the animal, metabolism of natural steroids again follows the endogenous pathways. Other steroids are mainly excreted without changes of the original steroid structure. It has been demonstrated, that compounds applied as esters have a delayed elimination. Anabolic agents of nonsteroidal structure, (group [c]) like stilbene derivatives and zeranol (6-[6, 10-dihydroxy-undecyl] beta-resorcylicacid-mu-lactone) are not, or only to a minor percentage, catabolized in the body. It can be generalized so far, that the fraction of the hormone eliminated in the urine, is in the conjugated from, while the fraction appearing in the feces is in the free form. This is due to enterohepatic circulation, which occurs with both, the intact or catabolized compound. The elimination rate of anabolic agents not only depends on the absorption after oral or parenteral application, which is strongly related to the type of formula---or cleavage of possible esters, but also on the metabolic clearance rate, which is a function of several factors, for example binding to plasma proteins or tissue structures. Differences in the elimination rate between compounds could be attributed to these phenomena. Tissue residue formation not only depends on the elimination rate, but also on other factors like mode of application, formula and withdrawal time. The possibility for their detection is related to the method applied. In cases of adequate treatments of the animals, and with the exception of the implantation site (see below), positive hormone values in tissues (qualitative and quantitative) could only be obtained, when radioimmunoassay techniques with a sensitivity in the low nanogram range were applied...
Anabolic Agents↗
The use of anabolic agents in HIV disease.
Anabolic steroids are synthetic analogues of the natural androgenic 'male' hormone called testosterone that is produced primarily in the testes in males and in the ovaries in females. Anabolic steroids and other agents are fast becoming part of the standard of care for HIV disease, gaining acceptance in reversing loss of lean body mass, increasing muscle strength, improving sexual functioning and appetite and creating a general sense of well-being. This article will review commonly prescribed anabolic agents, discuss potential side effects and contraindications.
Anabolic Agents↗
Validation of a GC-MS screening method for anabolizing agents in aqueous nutritional supplements.
A sensitive and selective method for the screening of anabolizing agents in aqueous nutritional supplements is described and validated. A total of 28 different anabolizing agents are screened for, including testosterone and prohormones, nandrolone and prohormones, stanozolol, and metandienone. The different analytes are extracted from the aqueous nutritional supplements by liquid-liquid extraction with a mixture of pentane and freshly distilled diethylether (1:1) after the supplements have been made alkaline with a NaHCO3-K2CO3 (2:1) buffer. The anabolizing agents are derivatized with a mixture of MSTFA-NH4I-ethanethiol (320:1:2) as routinely used for the screening of anabolic steroids extracted from urine. The derivatives are analyzed by gas chromatography (GC)-mass spectrometry (MS) in the selective ion monitoring mode. The limits of detection range from 1 to 10 ng/mL. One aqueous nutritional supplement (creatine serum) was analyzed with this screening method and was found to contain dehydroepiandrosterone (DHEA) at very low concentrations. The presence of DHEA could be confirmed with GC-MS-MS. Results of the application of this method and a similar method for solid nutritional supplements previously described are given.
Anabolic Agents↗
[Studies on anabolic agents. I. Comparative study of the anabolic action of methandrostenolone (MA) and of 19-nortestosterone phenylpropionate (NTP) in the same individuals. II. Anabolic action of a depot form of methandrostenolone].
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Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture.
Muscle cell culture (L6) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effects of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 microM compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of [3H] leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using [3H] leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased (P less than .05) protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate (P less than .01) in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes (P less than .05) by dexamethasone, but increased (P less than .01) in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 microM level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle.
Anabolic Agents↗
[Toxicological aspects of the use of hormones as anabolic agents (author's transl)].
The use of anabolic agents may give rise to residues in foods of animal origin and thus to potential effects on public health. Therefore, the physiology, metabolism and toxicity of the three endogenous hormones. 17 beta-oestradiol, progesterone and testosterone are discussed. In addition, the effects of the use of three exogenous hormones, diethylstilboestrol (DES), trenbolone and zeranol are evaluated. As can be expected all six compounds have effects on the endocrine system and reproduction. Endogenous hormones and DES are teratogenic at high-dose levels. With the exception of DES, there is no evidence of a mutagenic action. 17 beta-Oestradiol and testosterone were shown to induce tumours at high-dose levels in experimental animals; probably however, a threshold can be established. The residues in edible tissue resulting from the use of endogenous hormones are much smaller than are the natural levels in cow's milk and butter. In view of the carcinogenicity of DES in man, its use should be strongly discouraged. A definite statement on the acceptability of the use of trenbolone and zeranol cannot be made.
Anabolic Agents↗
Anabolic Agents for Osteoporosis : What is Their Likely Place in Therapy?
Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving other bone qualities in addition to increasing bone mass. Teriparatide (human parathyroid hormone[1-34]) has clearly emerged as a major approach for selected patients with osteoporosis. Teriparatide increases bone mineral density and bone turnover, improves bone microarchitecture, and changes bone size. The incidence of vertebral and non-vertebral fractures is reduced. Teriparatide is approved in many countries throughout the world for the treatment of both postmenopausal women and men with osteoporosis who are at high risk for fracture. Another anabolic agent, strontium ranelate, may both promote bone formation and inhibit bone resorption. Clinical trials support the use of strontium ranelate as a treatment for postmenopausal osteoporosis and have shown that strontium ranelate reduces the frequency of vertebral and non-vertebral fractures. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, growth hormone, and insulin-like growth factor-I, have been examined, although less data are currently available on these approaches.
Anabolic Agents↗
Anabolic agents in trauma and sepsis: repleting body mass and function.
Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are potent anabolic agents. Exogenous GH improves nitrogen metabolism in patients undergoing surgery; however, the anabolic effects of GH in cases of multiple injury, burn, and sepsis are equivocal. Moreover, few data are available concerning the effects of GH in organ failures. Exogenous IGF-1 attenuates catabolism in animal trauma models. A clinical trial, however, did not confirm the anabolic actions of IGF-1. Further knowledge of the interaction between the GH/IGF-1 axis in critical illness is essential for GH and IGF-1 therapy. Theoretically, the improved nitrogen metabolism achieved with exogenous anabolic agents may provide functional benefits. However, only a few studies have confirmed the beneficial effects of GH on body function in trauma and sepsis. GH treatment decreases the postoperative depression of hand grip strength. GH also stimulates wound healing. Both GH and IGF-1 exert their effects on immune system, suggesting that these anabolic agents are potentially beneficial for the prevention and treatment of sepsis. On the contrary, inhibition of polymorphonuclear neutrophil apoptosis and the potentiation of PMNs by GH may have harmful effects on the systemic responses. Further studies are required to determine the safety and clinical benefits of GH administration in critical illness.
Animals↗