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牛体内内源性和外源性合成代谢剂的代谢

Metabolism of endogenous and exogenous anabolic agents in cattle.

作者信息

Rico A G

出版信息

J Anim Sci. 1983 Jul;57(1):226-32. doi: 10.2527/jas1983.571226x.

Abstract

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.

摘要

内源性合成代谢剂,如雌二醇-17β、孕酮和睾酮,都是类固醇,它们在肝脏中会迅速代谢,口服时活性不是很强。雌二醇-17β在牛体内以游离雌二醇-17α的形式经胆汁排泄,在猪体内则以葡萄糖醛酸苷和硫酸盐的形式经尿液排泄。在反刍动物中,孕酮的主要代谢产物是孕二醇,睾酮的主要代谢产物是表睾酮。在马体内,这些化合物的代谢产物主要是17-酮类固醇。内源性合成代谢剂的酯会迅速水解,未酯化的形式遵循与动物生物合成的天然化合物相同的生物转化途径。外源性合成代谢剂,如醋酸群勃龙、玉米赤霉醇和己烯雌酚,口服时可能具有活性,并且在肝脏中的代谢比内源性合成代谢剂更慢。它们的代谢途径可能很复杂,并在与葡萄糖醛酸结合后形成排泄形式。关于生化作用机制,可以假定合成代谢剂通过细胞内受体的方式像所有类固醇一样发挥作用。生物转化可能会产生更具反应性的分子,这些分子可能会与生物体的正常成分结合。结合型代谢产物通常比游离型代谢产物形成得晚,并且被认为毒性较小,生物利用度较低。

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