During the course of fifty years, anabolic steroids have become well renowned for their safe and effective growth-promoting activities that work in improving muscle leanness, augmenting the daily average gain, the moderate stimulation of the feed intake, and consequently improving the feed efficiency, which is the gain rate in relation to the quantity of feed required to attain such gain. It is therefore unsurprisingly common that over ninety percent of the total feedlot cattle in the United States alone have received some sort of steroidal implant throughout their lifetime. (NAHMS, USDA 2000)
Anabolic agents may be administered into the cattle via one of the two most common routes; the first being an oral intake where the agent is integrated into the concentrate feed, such as the newly FDA approved Beta agonists that pref¬erentially works at increasing carcass lean tissue by the end of feeding period. While the second route pertains to the use of subcutaneous slow releasing implants containing trenbolone acetate (testosterone analogue) or combined preparations of androgens and estrogens, where TBA/E2 implants are the most prominently used (Heitzman,1976). Generally, such implants have been shown to increase the growth rate from 8% to 28%, improve feed effi¬ciency by 15% and enhance carcass lean tissue mass from 3 to 10 percent. (Duckett and Owens, 1997).
Such enhancements have generated remarkable production benefits for the beef industry, especially in productiv¬ity, which is the amount of beef produced per animal.
Therefore benefits arising from feed efficiency improvements starts by a drastic decrease in production costs by lessening the quantity of food supply needed per unit of gain. Furthermore, consumers would still obtain the same amount of food even though less land is being used. Greenhouse gases production would become restrained when the amount of animals needed to produce the same quantity of beef is reduced. (Avery and Avery, 2007) Moreover, another added benefit for improving feed efficiency is through providing consumers an affordable beef supply at lower costs. (Lawrence and Ibarburu, 2009).
One of the main advantages for steroidal implant use is the improvement of protein accumulation (lean tissue deposits) within the carcass. Therefore, retail product cost per head may be increased up to $100 due to the improvements in lean tissue deposition (Hancock et al., 1991). Moreover, since the growth composition of meat is modified and altered more towards lean tissue than for adipose tissue, a much healthier nutrient-rich product with subsequently less calories is produced.
Since animal products contribute significantly to the total caloric and nutri¬ent intake in the human population, altering the composition of growth toward more lean tissue and less adipose tissue results in a healthier product with fewer calories that still is rich in benefi¬cial nutrients.
The New Animal Drug Application (NADA) process are responsible for testing the majority of growth-promoting com¬pounds before finally being approved off and mandated by the FDA. Such procedures are quite methodical and systemic; therefore they are managed and supervised by scientists at the FDA’s Office of New Animal Drug Evaluation within the Center for Veterinary Medicine (CVM). The authorization of a new growth –promoting drug is granted, only if a standard 75 independent studies that document certain health safety regulations such as human food safety, animal safety, efficacy, environmental safety, and user safety, are met.
The classification of compounds:
Anabolic steroids:
Estrogens, androgens, and progestins are of the widely used anabolic steroids that can be either naturally occurring or synthetic. The natural hormones are found in all mam¬malian species regardless of gender. Whereas the three most commonly used synthetic compounds in beef cattle production are zeranol, trenbolone acetate,and melegestrol acetate, with the resultant growth rate and feed ef¬ficiency enhancement..
Zeranol, a nonsteroidal macrolide and is a naturally occurring ?-resorcyclic acid lactone, which was initially isolated from corn mold. Even though a non-steroid by nature, it has yet maintained in demonstrating estrogen-like biological behaviors in cattle.
Trenbolone acetate (TBA) (1967), is a testosterone analogue with 10 to 50 times the anabolic activity of testos¬terone (Bouffault ; Willemart, 1983). It is often used in combination with an estrogen (mainly E2) to maximize growth rate and efficiency in cattle, especially in steers. During 2008, nearly two-thirds of all implants marketed in the U.S. were estimated to be single implants of different TBA and E2 (TBA/E2) concentrations. Therefore, TBA and E2 at var¬ious concentration levels remain the most widely used type of growth-promoting implants in the industry.
Melengestrol acetate (MGA) is accepted for the use in feedlot heifers for estrus suppression and growth efficiency enhancement. Although an exogenous, synthetic progestin, however melengestrole acetate with its unique characteristics would al¬low it to become active once fed to heifers at 0.40 mg/head/day, therefore it highly unnecessary to administer this compound as an implant. Cattle producers can safely feed this product until harvest, due to its rapid metabolism by the animal, with no detectable traces in edible tissues, and hence a non-existing withdrawal period. At present, MGA is permitted for feedlot heifers only and therefore prevent from feeding it to steers.
With the exception of MGA, which is orally active, the remainder of anabolic steroids are introduced in the form of compressed pellet-implants with a variety of inert carrier compounds. Proper implanting of such compounds is equally important for efficacy as well as for safety. The implants are administered in the back of the middle of the ear of cattle, where the active steroids would start dissolving slowly into the blood¬stream of the ear. Special binding proteins then transport the compounds throughout the bloodstream and distribute it to various body tissues.
Cattle steroidal implants
?-adrenergic agonists:
The United States is one of several countries that have approved for the use of ?-adrenergic agonists (?-AA), classified as phenethanolamine compounds, in animal-food production. They are neither steroids nor peptide growth factors; however they are quite similar to the endog¬enous catecholamines; norepinephrine and epinephrine, which are found in all mammalian species including humans.
Ractopamine hydrochloride and zilpa¬terol hydrochloride are both approved as growth promotants for beef cattle. Ractopamine therefore helps improve weight gain, feed efficiency, and increase leanness in cattle and especially in pigs. ). The brand names for ractopamine are Paylean for pigs and Optaflexx in cattle, while Zilpa¬terol is marketed as Zilmax. In both cases, these compounds are orally active in the parts per million (ppm) concentra¬tion range, and are fed at the very end of the feeding period, immediately prior to harvest (last 20 to 42 days).
Ractopamines Zilpaterole
Other types of growth promotants that are used (non-steroidal):
Recombinant bovine somatotropin (rbST):
It is also known as growth hormone, a natural protein hormone produced by the pituitary gland. In dairy cows, bovine somatotropin (bST) is a major regulatory hormone of milk production. (Etherton et al,1998). The recombinant type (rbST) is a man-made version of bovine somatotropin which is introduced into cows via shots and that helps increase amount of milk production. There is no FDA-approved test that can differentiate milk of rbST treated cows from the milk of non-rbST treated cows (Raymond, 2009). Milk production is therefore enhanced by an average of around 15 percent in US dairy cows, which would reduce milk production costs, thus rendering it much affordable for consumers.
Ionophores:
Ionophores such as monesin, lasalocid, laidlomycin, salinomycin, and narasin are antimicrobials commonly fed to ruminants for feed efficiency improvements (Callaway et al., 2003). Antimicrobials work by targeting and altering gut (stomach) bacteria so that food can be better digested. Therefore Ionophores function by negatively affecting gram-positive bacteria and protozoa metabolism in the rumen. Such bacteria are the ones that would usually lead to a decline in efficient rumen digestive physiology and energy supplied from the ruminal digestion of feedstuffs. Such alterations would eventually lead to a less generation of waste products such as methane (Guan et al. 2006) and a decrease in ruminal protein breakdown, resulting in less ammonia produced. This shift that took place towards the more beneficial bacteria, increased propionic acid levels and decreased acetic and lactic acid production, thus increasing cattle overall energy status and an enhanced feed efficiency use. Monensin is widely marketed as Rumensin and plays a role in increasing milk production efficiency. Moreover, Inophores are also used to increase beef cattle weight gain and to decrease the time taken to reach market weight.
Monensin for cattle
Subtherapeutic use of antibiotics:
Low doses of antibiotics are used as “growth promotants” in animal feeds and are therefore considered to improve product quality with a lower fat percentage and higher protein content in meat (Hughes et al., 2002). This may also be reffered to as a “subtherapeutic” use because the antibiotics in this case are used to improve overall growth and health, instead of curing a specific disease.
The mode of action of implants:
TBA/E2 implants
Combined TBA/E2 implants increase carcass protein by approx¬imately 10% when compared to non-implanted steers, in which most of it takes place the first 40 days following implantation. Anabolic steroids may play a direct effect of inducing muscle hypertrophy by diffusing through the plasma membrane of muscle cells and binding to cytoplasmic receptors, where the complex enters the nucleus binds DNA and acts as a transcription factor. The proteins expressed are actin and myosin which are the basic units of muscle filaments incorporated into muscle fibers. However anabolic steroids may also have an indirect effect on muscle cells via the production and the circulation of IGF-1. Insulin like growth factor IGF-1 produced mainly by the liver, is a potent stimulator of skeletal muscle growth and differentiation. It is therefore thought to stimulate skeletal muscle protein synthesis and re¬duce skeletal muscle protein degradation. Several experiments have shown an increase of circulating IGF-1 and skeletal muscle IGF-1 mRNA levels in TBA and estradiol-17? (TBA/E2) implant treated cattles than in the non-treated control steers.
Moreover, TBA/E2 introduction into steers resulted in an increase in the number of actively proliferat¬ing satellite cells within 35 days of implantation, therefore increased proliferative activity of satellite cells (muscle cells precursors) should increase the rate of skeletal muscle growth in cattle. Such effects may be observed within days after im¬plant administration. Stimulus for early muscle growth is primar¬ily hypertrophic (increased cell size), which has been realized via depressed DNA to protein ratios. However, hyperplasia (increase in cell #) occurs only after an extended or long (weeks) exposure to the com-bined estrogenic/androgenic implants, therefore detected through the in¬crease of the satellite cell nuclei. In such case, the amount of muscle protein is enhanced with normal DNA/protein ratio is detected, which indicates that proliferation of satellite cells resulted in increased quantity of DNA in the muscle. Further cell culture studies have shown that the mitogenic activity of sera is increased, supporting the fact that implants initially increase hypertrophy and then would eventually increase hyperplasia to support corresponding increased in muscle mass.
