Progesterone precursor

A case with a deficiency in 17a-hydroxylase has been described. In such a case, the biosynthesis of either 17-pregnenolone (precursors of 17-ketosteroid) or 17-progesterone (precursors of cortisol) is impossible. Consequently, there is a decrease in the biosynthesis of androgens, estrogens, and cortisol. 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

Pregnenolone and Progesterone Are the Precursors of All Other Steroid Hormones... 

Progesterone Receptor. Prepro-opiomelanocortin (POMC) is a huge precursor... 

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 precursor 3 served as a starting material for a series of trisubstituted thiophenes in a study towards progesterone receptor modulators, giving for example the product 4 upon reaction with an appropriate bromoketone. The fact that rather complex thiophene derivatives could be prepared in a straightforward manner compensates for the low overall yields <06JHC1391>. 

Pregnenolone leaves the mitochondria to become the obligatory precursor of corticosteroids and adrenal androgens. The biosynthetic pathway next branches into two separate routes. One route passes through progesterone and corticosterone to aldosterone, and the other... 

Several compounds have been developed that inhibit the 17-hydroxylation of progesterone or pregnenolone, thereby preventing the action of the side chain-splitting enzyme and the further transformation of these steroid precursors to active androgens. A few of these compounds have been tested clinically but have been too toxic for prolonged use. As noted in Chapter 39, abiraterone, a newer 17-hydroxylase inhibitor, may prove to be clinically successful. 

Biosynthesis of progesterone. Desmolase is found in the mitochondria of steroid-producing tissues. Cholesterol is converted to pregnenolone in the mitochondria and then transferred to the endoplasmic reticulum, where it is converted to progesterone. Progesterone is a hormone as well as the precursor of several other hormones. 

Powdered Dioscorea (wild yam) root or extract is also marketed to treat the symptoms of menopause as an alternative to hormone replacement therapy (see page 279). Although there is a belief that this increases levels of progesterone, which is then used as a biosynthetic precursor of other hormones, there is no evidence that diosgenin is metabolized in the human body to progesterone, and any beneficial effects may arise from diosgenin itself. 

Small quantities of progesterone, testosterone, and estradiol are also produced by the adrenal gland. However, they play a minor role compared to the testicular and ovarian hormones. Progesterone, which is the precursor of cortisol, aldosterone, testosterone, and estradiol, is synthesized from 5-pregnenolone by 3-P-ol-dehydrogenase. Deficiency of this enzyme results in cortisol and aldosterone deficiencies. Such patients require replacement therapy with both glucocorticoids and mineralocorticoids. 

Progesterone is not only an important progestin, but is also an important precursor for androgen. It is synthesized according to the following scheme ... 

Progesterone is the most important progestin in humans. In addition to having important hormonal effects, it serves as a precursor to the estrogens, androgens, and adrenocortical steroids. It is... 

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