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Hormones: Anabolic AgentsHugh GalbraithUniversity of Aberdeen, Aberdeen, U.K.INTRODUCTIONGrowth in animals is well known to be influenced by arange of endogenous anabolic compounds that promotecommercially desirable greater lean tissue deposition andreduced fat in body tissues. These compounds, which actdirectly or indirectly to alter anabolic or catabolic pro-cesses, include protein hormones and growth factors andsteroidal androgens and estrogens. Of these only andro-genic and estrogenic compounds along with certain pro-gestagens have been approved for commercial applicationin farm animals. This long-standing practice now mainlyapplies to beef production in North American countries. Incontrast, the European Union has applied the ''precau-tionary principle'' and prohibited both the use of thesepreparations internally and importation of meat fromtreated animals from external countries. This prohibitionis frequently questioned on the grounds of the smallamounts of residues consumed in beef in relation toendogenous quantities in humans and those determined assafe by toxicological methodology. This review willconsider, for the anabolic agents in commercial use,application and responses in practice, mode of action,residues, and contemporary issues relating to risk assess-ment for human consumers and the general environment.APPLICATION, PROPERTIES, ANDCONSUMER ISSUESCommercial Preparations, Hormone Delivery,Responses, and Mode of ActionThe anabolic preparations available in the United States[1]contain naturally occurring testosterone (T) and itspropionate ester, estradiol-17b (E) and its benzoate ester,progesterone (Pr), and the xenobiotic compounds trenbo-lone acetate (TA), zeranol (Z), and melengestrol acetate(MGA). Active ingredients may be further characterizedas estrogens (E is a steroid hormone synthesized mainly ingonadal tissues; Z is a resorcylic acid lactone derivative ofthe nonsteroidal fungal estrogen zearalenone), steroidalandrogens (T is a hormone synthesized in gonads andadrenal cortex with potential for conversion to estrogens;TA with effects produced mainly by its active metabolitetrenbolone-17bOH, exhibits both androgenic and anti-corticosteroid properties), and progestagens (naturallyoccurring steroid Pr; synthetic steroidal compoundMGA). Formulations containing single, or certain combi-nations of, ingredients are applied as impregnated silasticrubber implants or compressed pellets under the skin of theupper surface of the ear, or for MGA, inclusion in the diet.The relative quantities of active ingredients (up to43.9 mg for E and 200 mg for T, TA, and Pr) in implants[1]reflect amounts required to produce effects in vivo. Theseresult in variably circulating concentrations of total E inthe range of 5 to 80 pg/ml with those for T, TA, and Pr inexcess of 250 pg/ml.[2]Typical improvements in growth,feed conversion efficiency, and carcass leanness havebeen summarized[2]in the range of 10 to 30%, 5 to 15%,and 5 to 8%, respectively, with greatest effects occurringin steers in the relative absence of endogenous sexhormones. Smaller responses occur in postpubertal heifersand bulls.[3]Estrogens are considered to have the greatestanabolic activity with potentiation by androgens and inparticular when combined with trenbolone acetate. Forimplants, the growth responses are affected by rates andquantities of systemic uptake of hormonal compoundsfrom the implant, their transport by carrier proteins suchas sex hormone binding globulin or serum albumin, andthe diffusion of free forms into target cells. These eventsprecede interaction with specific members of the steroidnuclear hormone family of receptor transcription factorsfor estrogens, androgens, and progestagens and associatedchaperone proteins.[4–6]These ligand-bound steroidreceptors form activated, usually dimer, complexes thatalong with co-activators bind to specific nuclear hormoneresponse elements. Depending on recognition sites, thesemay activate or repress DNA expression to affect genetranscription and translation directly in skeletal muscle oradipose cells or indir

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