**1.1.4 Trenbolone acetate**

Trenbolone acetate (TBA) is a synthetic steroid with an anabolic potency that may exceed that of testosterone. It is a prodrug that converts into its active form 17β-trenbolone, which isomerises into 17α-trenbolone.

17β-trenbolone is the major form occurring in muscle tissue, whereas the 17α-epimer is the major metabolite occurring in liver and in the excreta including bile. It is assumed to exert its anabolic action via interaction with androgen and glucocorticoid receptors (Danhaive and Rousseau, 1986, 1988). Experiments with cattle tissues have shown that 17β-trenbolone binds to the androgen receptor with similar affinity as dihydrotestosterone. It also binds to the progesterone receptor with an affinity that exceeds that of progesterone. The other metabolites of TBA, including 17α-trenbolone (17α-hydroxy-estra-4,9,11-trien-3-one) and TBO (estra-4,9,11-triene-3,17-dione) show a significantly lower binding affinity to both types of receptors (Bauer *et al.,* 2000).

Reports regarding the (mis)use of TBA as an anabolic agent in sports people describe several adverse effects, including liver cell injury with an increase in liver-specific enzymes in serum, cholestatic jaundice, peliosis hepatitis and various neoplastic lesions. Moreover, decreased endogenous testosterone production and spermatogenesis, oligospermia and testicular atrophy may be associated with the repeated use of TBA as anabolic (Bahrke and Yesalis, 2004; Maravelias *et al.,* 2005).

### **1.1.5 Zeranol**

36 A Bird's-Eye View of Veterinary Medicine

activation and/or suppression of specific gene transcription in target organs. Androgen receptors are detected in tissues of females, as well as males. The presence of this receptor in organs such as the ovary indicates significant activity of androgens in both sexes. Furthermore, the androgen receptor is thought to be involved in ovarian tumorigenesis, as it has been detected in 67 percent of ovarian tumors. Although current information indicates the presence of only a single androgen receptor, it is known that different subsets of genes

In animals, testosterone or testosterone propionate, alone or in combination with other hormonally active substances, is used primarily to improve the rate of weight gain and feed efficiency. This effect is most likely a consequence of the anabolic action of androgens.

Progesterone is synthesized and secreted mainly by the corpus luteum in the ovary of

As all hormones, progesterone synthesis and secretion is regulated by a series of positive and negative feedback mechanisms in which polypeptidic hormones secreted by the brain

Progesterone and synthetic progestins are used pharmacologically in women in conjunction with ovulation stimulation drugs as well as during early pregnancy in cases of luteal phase dysfunction. Although results have been conflicting, some studies find an association between pregnancy-related intake of progestins and increased risk of hypospadias (congenital malformation of the urethral opening on the penis) in the male offspring (Carmichael *et al.,* 2005). It should however be noted that this was observed in relation to pharmacological doses of progestins, and as progesterone levels are normally high during pregnancy, minor additional exogenous progestagenic activity would presumably be without significant effects in the presence of a high endogenous activity, unless the synthetic progestins act at different sites and by different mechanisms. In contrast, serum levels of progestins in children and postmenopausal women are very low. Data on effects of progesterone in the prepubertal child are scarce and no new data have been identified. Likewise, no animal studies on the effects of progesterone during the postnatal development

It is well established that progesterone not only serves as the precursor of all the major steroid hormones (androgens, oestrogens, corticosteroids) in the gonads and adrenals, but also is converted into one or more metabolites by most tissues in the body (Wiebe, 2006).

Trenbolone acetate (TBA) is a synthetic steroid with an anabolic potency that may exceed that of testosterone. It is a prodrug that converts into its active form 17β-trenbolone, which

17β-trenbolone is the major form occurring in muscle tissue, whereas the 17α-epimer is the major metabolite occurring in liver and in the excreta including bile. It is assumed to exert

may be activated by either testosterone or DHT (Chang *et al*., 1995).

cycling females, and, during pregnancy, by the placenta.

(hypothalamus, pituitary) affect circulating progesterone levels.

**1.1.3 Progesterone** 

have been published recently.

**1.1.4 Trenbolone acetate** 

isomerises into 17α-trenbolone.

Zeranol is derived from the naturally occurring mycoestrogen zearalenone, and is a potent oestrogen receptor agonist *in vivo* and *in vitro* (Leffers *et al.,* 2001; Le Guevel and Pakdel, 2001; Takemura *et al.,* 2007; Yuri *et al.,* 2006). Its actions resemble those of oestradiol. (Leffers *et al.,* 2001).

Zeranol stimulates the proliferation of ER-dependent cell proliferation in MCF-7 human breast cancer cells (which are widely used in the assessment of estrogenic activity) and in transfected cells (Leffers *et al.*, 2001; Le Guevel and Pakdel, 2001; Liu and Ling, 2004).

It is used alone or in combination with TBA as a hormonal growth promoter in various products.
