Testosterone active metabolites

Figure 53-3 Pathways of peripheral metabolism of plasma testosterone.Testosterone can be metabolized either to active metabolites or to excretory metabolites. (From Griffin JE,Witson JD.

A fruit extract has been shown to selectively antagonize and prevent binding to 52% of dihydrotestosterone receptors in the pros-tate. Oral administration of a fruit extract in mice and rats has demonstrated inhibition of up to 90% of the activity of prostate 5-a-reductase (that transforms testosterone into metabolites increasing the size of the... 

The primary and most important androgen is testosterone. In the adult male, its active metabolite dihydrotestosterone supports spermatogenesis for reproduction as well as maintaining muscle mass and fat distribution. Estrogens are associated with development of female secondary sex characteristics and comprise of estrone, estradiol, and estriol. Steroid hormones are not exclusively gender specific and have important roles in both males and females. 

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

Ester hydrolysis does not invariably lead to inactive metabolites, as exemplified by acetylsalicylic acid. The cleavage product, salicylic acid, retains pharmacological activity. In certain cases, drugs are administered in the form of esters in order to facilitate absorption (enalapril enalaprilate testosterone undecanoate testosterone) or to reduce irritation of the gastrointestinal Lullmann, Color Atlas of Pharmacology... 

When rats were administered atrazine in drinking water at 0.1, 0.2, or 0.5 g/1 for 1 or 3 weeks, they excreted as the principal metabolite 2 -chloro-4-ethylamino-6-amino-s-triazine. Atrazine and its metabolites have been shown to alter the activity of some testosterone-metabolizing enzymes in the rat pituitary and hypothalamus and to decrease hormone-receptor binding in the prostate. ... 

Testosterone metabolism. The lipido-ste-rol extract (LSESr, Permixon) was studied in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy and prostate cancer tissues. The extract inhibited the formation of the T metabolites androstenedione 5 4 and 5 a-DHT The lipophilic extracts of fruits inhibited T 5p-reductase (EC 1.3.99.5) (5(xR). For fatty acid-like 5(xR inhibition a strongly polar end-group and a molecular skeleton allowing nonpolar interactions with the enzyme were required. The result indicated that 5pR activity in prostatic tissue may be influenced by the lipid environ-... 

Testosterone, when administered by mouth, is rapidly absorbed. However, it is largely converted to inactive metabolites, and only about one sixth of the dose administered is available in active form. Testosterone can be administered parenterally, but it has a more prolonged absorption time and greater activity in the propionate, enanthate, undecanoate, or cypionate ester forms. These derivatives are hydrolyzed to release free testosterone at the site of injection. Testosterone derivatives alkylated at the 17 position, eg, methyltestosterone and fluoxymesterone, are active when given by mouth. 

Trenbolone acetate is a synthetic steroid with hormonal activity similar to testosterone but with greater anabolic activity. After administration to cattle, trenbolone acetate is rapidly hydrolyzed to its free hydroxylated form (28). The 17 -OH epimer is the major metabolite occurring in the excreta, bile, and liver. 

The step-by-step synthesis of the steroid hormones pregnenolone and progesterone from cholesterol (C27) was presented in chapter 20 (see fig 20.22). Note that pregneno-lone (C2i) and progesterone (table 20.4) (C2 ) are intermediates in the biosynthesis of all of the major adrenal steroids, including cortisol (C2i), corticosterone (C21), and aldosterone (C21). The same two compounds are intermediates in the synthesis of the gonadal steroid hormones, testosterone (C,9) and 17/3-estradiol (CI8). Because the synthesis of all these hormones follows a common pathway, a defect in the activity or amount of an enzyme along that pathway can lead to both a deficiency in the hormones beyond the affected step and an excess of the hormones, or metabolites, prior to that step. 

---