Androstenedione, from

The intermediate 5-en-3-oxosteroids, such as 5-androstenedione (from DHA) are further converted by isomerization to the 4-en-3-oxosteroids by means of the 4,5-isomerase. This enzyme, which requires no cofactor, is associated with the smooth... 

Figure 9.129 Amount of hydroxylated reaction product formed by 0.75 mg of hepatic microsomal protein in 1.0 mL of reaction mixture incubated at 37°C for different lengths of time. 2a, 6jQ, 7a, and 16a-OHT are the hydroxylated metabolites of testosterone A is androstenedione. (From van der Hoeven, 1984.)...

Occurrence other than in man The spectrum of A. in vertebrates is, in principle, qualitatively the same as that in humans although there may be quantitative differences and differences with regard to biosynthetic and metabolic details. A. have also occasionally been isolated from plants as metabolites of steroidal secondary substances, e.g., testosterone and androstenedione from pollen of Scottish pine Pinus sylvestris (Pin-aceae) and rubrosterone (2/3,3/S,14a-trihydroxy-5)8-androst-7-ene-6,17-dione), a biological degradation product of an ecdysteroid from Achyranthes rubro-fusca (Amaranthaceae). 

One interest in inhibition of P450 17A1 is treating prostate cancer. The corrcept is that prostate cancer is stimulated by androgerrs, and the goal is to block production of androstenedione (from progesterone/17a-hydroxyprogesterone). This is a particular issue in castration-resistant prostate cancer. 

In the placental tissue, there is an extensive formation of androstenedione from dehydroepiandrosterone, which is obtained mostly by the hydrolysis of dehydroepiandrosterone sulfate, which is biosynthesized principally in the fetal compartment. On the other hand, as was indicated before (Section 111, B, 1, a), in the placental compartment very few if any Cw steroids arc formed from Cm steroids by side-chain cleavage (Warren and Cheatum, 1964 Jaffe et al., 1965). Also, since androstenedione is not a good substrate for 17d-rcductasc, it can be assumed that most of the placental t( Stosterone originates from fetal androstenediol (Uell Acqua et al., 1966, 1967a,b). It is interesting to note that thi.s latter steroid is a normal const.ituent of cord blood (Kberlein, 1965). 

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

Sex Hormones Testosterone and androsterone are the two most important male sex hormones, or androgens. Androgens are responsible for the development of male secondary sex characteristics during puberty and for promoting tissue and muscle growth. Both are synthesized in the testes from cholesterol. Androstenedione is another minor hormone that has received particular attention because of its use by prominent athletes. 

Estrogens are formed by the aromatization of androgens in a complex process that involves three hydroxyla-tion steps, each of which requires O2 and NADPH. The aromatase enzyme complex is thought to include a P450 monooxygenase. Estradiol is formed if the substrate of this enzyme complex is testosterone, whereas estrone results from the aromatization of androstenedione. 

Testosterone, the major androgenic hormone, accounts for 95% of the androgen concentration. The primary source of testosterone is the testes however, 3% to 5% of the testosterone concentration is derived from direct adrenal cortical secretion of testosterone or C-19 steroids such as androstenedione.17,18... 

FIGURE 4.82 Mechanism for the formation of estrone from androstenedione by aromatase. 

Protein identified by IHC in the ventral pallidum, cerebral cortex, the amygdaloid area, the nucleus of the diagonal band, others of rat brain (Shinoda et al., 1989). Less activity in human fetal brain than other tissues assayed by pH] release from 1-androstenedione into water (Doody and Carr, 1989). 

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-... 

Steroids that aid in muscle development are called anabolic steroids. They are synthetic derivatives of testosterone, thus have the same muscle-building effect as testosterone. There are more than 100 different anabolic steroids which, vary in structure, duration of action, relative effects and toxicities. Androstenedione, stanozolol and dianabol are anabolic steroids. They are used to treat people suffering from traumas accompanied by muscle deterioration. The use of anabolic steroid can lead to a number of dangerous side-effects, including lowered levels of high density lipoprotein cholesterol, which benefits the heart, and elevated levels of harmful low density lipoprotein, stimulation of prostate tumours, clotting disorders and liver problems. 

In men, approximately 8 mg of testosterone is produced daily. About 95% is produced by the Leydig cells and only 5% by the adrenals. The testis also secretes small amounts of another potent androgen, dihydrotestosterone, as well as androstenedione and dehydroepiandrosterone, which are weak androgens. Pregnenolone and progesterone and their 17-hydroxylated derivatives are also released in small amounts. Plasma levels of testosterone in males are about 0.6 mcg/dL after puberty and appear to decline after age 50. Testosterone is also present in the plasma of women in concentrations of approximately 0.03 mcg/dL and is derived in approximately equal parts from the ovaries and adrenals and by the peripheral conversion of other hormones. 

Fig. 4. The gonadotrophin two-cell model of ovarian steroidogenesis involves the stimulation of thecal cells by LH to produce androstenedione and testosterone while FSH stimulates granulosa cells to synthesize estrogens from the theca-derived androgens.

In the placenta, there are 17P-HSDs that reduce androstenedione to testosterone (in rodents) and estrone to estradiol (in rodents and humans) and 17P-HSDs that promote the opposite activity, possibly protecting the fetus from highly active hormones (Peltoketo et al.,... 

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