As-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... 

The ovary normally ceases its gametogenic and endocrine function with time. This change is accompanied by a cessation in uterine bleeding (menopause) and occurs at a mean age of 52 years in the USA. Although the ovary ceases to secrete estrogen, significant levels of estrogen persist in many women as a result of conversion of adrenal and ovarian steroids such as androstenedione to estrone and estradiol in adipose and possibly other nonendocrine tissues. 

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. 

Higashi and coworkers [28] used 2-hydrazino-l-methylpyridine (HMP) derivatization to introduce a positively charged moiety in testosterone and dihydrotestosterone (DHT) to achieve a sensitivity improvement of 70- to 1600-fold compared to underivatized molecules in ESI. However, they found the derivative was unsuitable for di-keto steroids such as androstenedione and progesterone, so this form of derivatization is unlikely to be widely accepted. Separable syn- and anti- (E and Z) stereoisomers are formed using this derivative. Preparation is as follows a solution of 10 pg HMP in 50 pi ethanol containing 25 pg TFA was added to the steroid dissolved in 30 pi ethanol. After heating for 1 h at 60 C, the solvents can be removed and sample injected. 

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-... 

The ceUular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone ro other steroid hormones (Figure 42-8). 

The 17P-hydroxysteroid oxidoreductase enzymes (HSOR) occur as two distinct isoforms (I and II). They are involved in the conversion of estrone to estradiol. The type I enzyme converts estrone to estradiol (also androstenedione to testosterone) and the type II catalyses the reverse reaction. Phytoestrogens have been shown to inhibit both HSOR enzymes in vitro. 

An interesting pair of compounds is caffeine and theophylline [97] these compounds are relatively polar compounds with different functional groups (tertiary and secondary amine). In a few cases, more appropriate comparisons have been made such as between androstenedione/testoster-one and methyl benzoate/anisole these compounds are expected to be different in Snyder interaction groups. 

Steroidal AIs have been synthesised using the structure of androstenedione as starting point for the chemical optimisation programme (Fig. 6). These inhibitors bind to the aromatase in the same manner as the substrate androstenedione. The structure-activity relationship (SAR) of the androstenedione derivatives has extensively been investigated. Although several of these... 

High-dose progestins are used as last-line endocrine therapy [223]. They inhibit the adrenal steroid biosynthesis. The decrease of estrogen levels is comparable to that caused by the administration of aromatase inhibitors. In post-menopausal women, the progestin megestrol acetate (MGA) decreases serum plasma level of DEAH, androstenedione and cortisol to less than 10% [223,224]. 

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. 

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