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Both the gonads and the adrenal cortex secret steroids with anabolic activity. It should be realized that the most intense anabolism occurs during infancy and childhood at which time the concentration of steroid hormones with anabolic activity is extremely low. By far the most important anabolic steroid is in testosterone followed by androstenedione, androsterone and dehydroepiandrosterone. Also, estrogens have a generalized anabolic effect, although these hormones have their greatest anabolic action in their respective target organs. In males, after a short period of relatively high T levels immediately after birth, T levels during infancy and childhood are low (+/- 20--30 ng/100 ml); the increase of T levels in one of the first objective signs of puberty and over a period of 3--4 years adult T levels are reached. The latter vary between 380 and 1,000 ng (mean 660 ng/100 ml); the increase in the protein-free, non-protein bound testosterone is even more impressive as the concentration of testosterone binding globulin decreases sharply at puberty. Testosterone levels remain constant up to the 7th decade of life, and decrease rapidly thereafter; free testosterone levels decrease already after the age of 40. T secretion rates in adult males vary between 4 and 10 mg/24 hrs (-/m: 6.6 mg/24 hrs); in males over 65 years the mean T secretion is 4.2 mg/24 hrs: this decrease is a consequence of a decrease in plasma levels and a slowing down of the metabolism. T in adult males originates practically exclusively from the testes. Decreased T levels and secretion rates are observed in hypogonadism and under stressful conditions (anaesthesia, anxiety, hangover, exhaustion, undernutrition) as well as ACTH stimulation. DHT levels parallel generally T levels. Androstenedions (A) in adult males originates in about equal parts from the testes and adrenals. Androstenedione production rates in adult males vary between 1.4--2.1 mg/24 hrs. Dehydroepiandrosterone (DHEA) levels are low in infants and young children. They increase in the immediate pre-pubertal period to reach adult levels after completion of puberty. ACTH as well as stressful situations increase DHEA levels. The mean DHEA production rate is +/- 70 mg/24 hrs. Androsterone is a metabolite of T, A, DHEA, and 170HP, and circulates in plasma essentially as the 3-sulphate and to a lesser extent as the 3-glucuronide. In females, androgen levels before puberty are grossly similar to levels in male children. Pre- and post-menopausal levels of T, DHT, DHEA and their rates of production are discussed. Estrogens have also some anabolic effects. Levels of estradiol (E2) and estrone (E1) in cycling and post-menopausal women are also given. In post-menopausal women E2 levels are extremely low. E2 production rates in post-menopausal women are of the order of 5--20 mug/24 hrs. Progesterone does not appear to have an anabolic effect...

The role of farm animals as converters of feed protein into protein edible for humans has often been criticized for the lack of efficiency of this process. In a series of 192 N-balance studies with veal calves it was found, however, that these animals convert at an early age even more than 70 percent of the feed protein into body protein. The deterioration of the N-conversion, so undesirable from a point of view of food production, is found when the animals grow older. With increasing age the conversion ratio went down to approximately 40-50 percent in our studies. This could only be explained by assuming a poorer efficiency of the intermediate metabolic processes with increasing age. For an increase of the production of edible protein from the available feed sources in the world, it is obviously of great importance to maintain the favourable conversion ratio of young farm animals for the longest possible time. The object of this paper is to consider whether and to what extent a positive effect on the efficiency of the protein formation can be exerted by the application of anabolic agents using the veal calf as a model. In the category of artificial estrogens we found DES to be effective in this respect. In the category of natural hormones testosterone and progesterone did not exert anabolic effects. The implantation of 17beta-estradiol improved the conversion of feed protein into body protein to approximately the same extent as DES. A combination of estradiol with testosterone tended to be more effective than estradiol alone. The more recently isolated agents zeranol and trenbolone did not lead to significant improvements in N-retention. A combination of trenbolone with estradiol improved N-retention better than any of the other treatments. The quantitative importance of the phenomena discussed for protein production is illustrated as follows. With the most effective treatment studied, the percentage of feed protein converted into body protein was increased during an experimental period of 38 days, from 39 percent in the control group to 58 percent in the treated group. There is no doubt that a further intensification of the research in this field is recommendable in order to create and study active agents combinining a high degree of efficacy with the absence of undesirable side effects for man and animals.

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...

In this review paper various aspects of protein synthesis and breakdown in skeletal muscle will be surveyed as an introduction to the more specialized topics concerned with anabolic agents and the production of muscle protein. The quantitatively important role of skeletal muscle in total protein and amino acid metabolism will be evaluated by considering the size, composition (RNA and protein) and metabolic activity of this tissue in mammalian organism. This will provide an initial basis for understanding how internal and external environmental factors may affect the rate of growth and final size of the muscle mass in the intact organism. The steps in protein synthesis, involving aminoacid activation, initiation, peptide chain elongation and termination will be described, with particular reference to the synthesis of protein in fibers of skeletal muscle. This account will include a review of the specificity of myofibrillar protein synthesis and the relationships between the biochemical aspects of protein synthesis and the structural organization of the muscle cell. The role of messenger RNA, tRNA and soluble protein factors in the regulation of muscle protein synthesis in the growing animal will be reviewed, together with a short account of the ways in which hormones may modulate the rate of protein synthesis in muscle cells. However, the available data do not lead to definite conclusions concerning the rate limiting step(s) in muscle protein synthesis or the quantitative significance of factors which affect them. The mechanisms and regulation of protein degradation and the role of degradation in the regulation of muscle protein content will also be discussed.

The growth of populations and the spread of urbanization, resulting in new agricultural structures, have entailed a concentration of livestock production and recourse to new techniques. Of some importance among these techniques is the enteric or parenteral administration of substances in very low doses. These substances include anabolic agents, some of which, like many natural feeds, exhibit hormonal activity. They may be divided into two classes: --those of the DES type, synthetic compounds non-existent in the natural state, --natural agents, which are normally distributed throughout the animal and human organism, and hence in food of animal origin---milk, meat, eggs. The compounds belonging to the second class may also be synthesized and the main toxicological consideration is that they then have to meet clear-cut standards of identity and purity. A compound belonging to the first class, diethylstilbestrol (DES), administered to rats in doses as small as 60 mug/kg of feed or even smaller, causes in general lower growth rates as well as alterations in the genital system and reproductive functions. In long-term experiments (12 months) using rats and mice and applying so-called toxicity "de relais" tests, developed and described by the authors, it also appeared that meat from calves in which DES pellets were implanted under normal rearing conditions, inhibits growth and reproduction in mice and rats fed a diet containing 20% of this meat. Studies in which the livers from treated calves constituted 6% of the diet of these two rodent species also led to the conclusion that fertility was impaired in the second reproduction test. The authors also recall cases of vaginal cancer observed in young girls whose mothers had been treated with DES during pregnancy. Compounds belonging to the second class (estradiol-progesterone and estradiol-testosterone) gave no evidence of harmful effects upon rats when mixed with their rations during short and medium-term trials. Similar results were obtained from studies with rats and mice fed a diet containing 20% veal or 6% liver of calves in which pellets of these natural hormones had been implanted. In these studies, which lasted 23--24 months with rats and 347 days with mice, the toxicity "de relais" test was applied under similar conditions to those undertaken using meat and livers of implanted calves. The report also refers to trenbolone and to "zéralénone" but no toxicity "de relais" tests were carried out with the meat and livers of animals treated with these substances. The authors reached the following conclusions: DES should not be used as an anabolic agent in livestock production. Natural hormones prepared through synthesis or otherwise could be used as anabolic agents in livestock production since no risk to the consumer has been witnessed when they were administered at doses similar to those used in the author's experiments. However, it is recommended that they should be applied under veterinary super

Estrogenic compounds are effective in stimulating live weight gains and improving feed efficiency of growing and finishing ruminants. With the proper use of diethylstilbestrol or estradiol, weight gain and feed efficiency are improved approximately 15 and 12 percent, respectively. The administration of estrogenic substances to finishing cattle or sheep results in heavier carcasses containing more protein and moisture and less fat. Estrogens do not appreciably affect rumen fermentation or digestibility of the diet but improve the utilization of the absorbed nutrients. Evidence to support the concept that the increased weight gained with estrogen treatment is the result of anabolic reactions includes a decrease in plasma urea, decrease in plasma levels of most of the essential amino-acids, decreased excretion of urea and total nitrogen in the urine and increased retention of nitrogen, phosphorus and calcium. There is no change in body water space or tubular reabsorption of urea in sheep treated with diethylstilbestrol to account for some of these observations. More direct evidence that estrogens exert their major influence on nitrogen metabolism in the body and more specifically on protein synthesis comes from an experiment where cattle fed diethylstilbestrol deposited 33 percent more protein and 18 percent less fat in body weight gain as compared with control animals. The use of the hormone resulted in a significant improvement in the efficiency of utilizing dietary protein for body gain and a slight decrease in the efficiency of converting dietary energy to body gain. Enlargement of the pituitary, thyroid and adrenal glands and higher plasma levels of growth hormone, insulin and glucose have been found in experiments designed to study the effect of estrogens on the endocrine system of ruminants. These studies, along with the observation that an intact pituitary gland is necessary for estrogens to increase nitrogen retention in sheep, support the theory that estrogens are anabolic in ruminants because of increased secretion of growth hormone by the anterior pituitary. If follows that the increased secretion of growth hormone results in increased blood glucose which then stimulates secretion of insulin. Both growth hormone and insulin would be stimulatory to protein synthesis. This theory of the mode of action is further supported by the findings that injections of growth hormone closely resemble the effects of diethylstilbestrol on nitrogen retention and blood metabolites in sheep.