Dehydroepiandrosterone biosynthesis

Cloutier M, Fleury A, Courtemanche J, Ducharme L, Mason JI, et al. 1997. Characterization of the adrenal cytochrome P450C17 in the hamster, a small animal model for the study of adrenal dehydroepiandrosterone biosynthesis. DNA Cell Biol 16 357-368. 

Fig. 9. Abbreviated steroid biosynthesis where DHEA = dehydroepiandrosterone and DHT = dihydrotestosterone.

Figure 42-5. Pathways of testosterone biosynthesis. The pathway on the left side of the figure is called the or dehydroepiandrosterone pathway the pathway on the right side is called the A" or progesterone pathway. The asterisk indicates that the 17a-hydroxy-lase and 17,20-lyase activities reside in a single protein, P450cl7.

FIGURE 52-6 Biosynthesis/metabolism of steroids in the CNS. The conversion of delta5P to dehydroepiandrosterone (DHA) is postulated but not demonstrated. D5P and DHA inhibit and 3oc,5oc-THP potentiates GABAa receptor function, as summarized in Figure 52-7. Solid arrows indicate demonstrated pathways dotted arrows indicate possible pathways. Metabolic inhibitors of enzymes are indicated by . (Redrawn from [12], with permission.)... 

Brown RC, Cascio C, Papadopoulos V. 2000. Pathways of neurosteroid biosynthesis in cell lines from human brain regulation of dehydroepiandrosterone formation by oxidative stress and beta-amyloid peptide. J Neurochem 74 ... 

The steroid Ci7(20)lyase is an enzyme that is involved in the biosynthesis of andro-stenedione and of dehydroepiandrosterone from progesterone and pregnenolone, respectively. As androgen and estrogen hormones are necessary for the growth of tumors, this enzyme is a potential therapeutic target for the treatment of prostate cancer and in hormone-dependent breast cancers. 

The intermediates employed in the biosynthesis of androgens belong to two structurally different chemical classes, a,)3-unsaturated ketones (progesterone) and /3,y-unsatui ated alcohols (pregnenolone and dehydroepiandrosterone). The biosynthetic pathways in the production of androgens are also different [390]. 

FIGURE 12.1 Biosynthesis of estrogens. Abbreviations DHEA, dehydroepiandrosterone El, estrone E2, estradiol T, testosterone DHT, dihydrotestosterone. Letrozole is an aroma-tase inhibitor, Finasteride is a 5a-reductase inhibitor. Androstane-3p,17P-diol (SPO) is an estrogenic steroid and its synthesis is blocked by 5a-reductase inhibitor, but not affected by aromatase inhibitor."... 

Fig. 7. Biosynthesis of placental estrogens. Sequence of some chemical reactions. Dehydroepiandrosterone sulfate (DS) to androstene triol-sulfate and estrone (Ei) to estriol (Em) take place only in fetal or maternal liver.

A very high sulfatase activity which permits the hydrolysis of the steroid ester. sulfates involved in estrogen biosynthesis. These ester sulfates arc mainlj dehydroepiandrosterone- and 16 -hydroxyde iydro-epiandrosterono-3 -sulfate. 

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