Endogenous sex steroids

For all these hormonal substances to exert their desired effect, the method of administration to the animal is most important. They can be administered to animals by intramuscular injections but some compounds can be also administered incorporated into the feeds. However, the best method is one in which they are administered in form of a subcutaneous implant in the ear. This allows for a controlled slow release of the active ingredients, exposing the animal to a constant stimulating effect of the anabolic agent. 

The overall rate of absorption of an anabolic agent from an implant can be influenced by a number of factors, including the technique of administration, total dosage given, integrity of the implant, presence of a second anabolic in the implant, implant size, shape, and hardness. Since at the end of the withdrawal period, up to 10% of the initial dose may still be found at the site of implantation, care should always be taken to discard this area at slaughter. 

Unlike in the United States where some anabolic hormonal-type growth promoters are permitted, use of these compounds, either natural or synthetic, as growth promoters in meat-producing animals has not been allowed in the European Union since 1988, due to potential adverse effects to human health. Nevertheless, many anabolic hormonal-type growth promoters are still used illegally in the European Union. 

The distribution of residues of anabolic hormonal-type growth promoters in animal tissues depends on their mode of metabolism and excretion. Residues are commonly found in muscle, fat, liver, kidney, and milk, as well as in urine, bile, and feces. In general, residue concentrations tend to be higher in the excreta than in tissues. Control of the abuse of these compounds is usually carried out through the analysis of edible tissues, injection sites, kidney, fat, urine, or even feces. In recent years, use of fecal samples has become of increasing importance because of their ease of collection in intensive livestock farming. 

Two female sex hormones, estradiol-17 and progesterone, and one male sex hormone, testosterone, are used as growth promoters on beef cattle (Fig. 7.1). By nature, they are all endogenous products playing an important role in controlling reproductive functions in humans and animals. When applied exogenously they will enter the same metabolic pathways as the endogenously produced molecules. 

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Ferrini, R. L., Barrett-Connor, E., Caffeine intake and endogenous sex steroid levels in postmenopausal women The Rancho Bernardo study, Am J Epidemiol, 144, 642, 1996. 

Fig. 7.1 Chemical structures of commonly used endogenous sex steroids.

Similarly to other endogenous sex steroids, residue levels of progesterone in edible tissues of treated animals were very low. Residue depletion studies (5) in steers showed progesterone levels of 0.4 ppb in muscle, liver, and kidney, and... 

Compounds that mimic the effects of sex steroids in some tissues, while at the same time can oppose endogenous hormone action in other tissues. 

CYP1B1 is also expressed in the fetus in multiple tissues, particularly in thymus, spleen, kidney, and adrenal. A null CYP1B1 phenotype in humans has been associated with appearance of primary congenital glaucoma. Consistent with an important endogenous role for this enzyme in development of the eye, CYP1B1—which, in addition to biotransformation of xenobiotics, is also capable of metabolizing retinoid and sex steroids—is expressed in embryonic ocular tissues. 

Steroids that possess angular methyl groups at both the 10 and 13 positions but which are devoid of acetyl side chains at the 17 position are usually classed as derivatives of the hypothetical hydrocarbon, androstane. The endogenous male sex hormones, such as, for example, testosterone, can all be classified as androstanes as will be noted below, the biological activity of compounds in this stmctural class goes beyond that narrow definition. 

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