Dehydroepiandrosterone androgenic activity

The earliest report of an isolated androgen was presented by Butenandt (10) in 1931. He isolated 15 mg of crystalline androsterone from 15,000 L of human male urine. A second crystalline compound, dehydroepiandrosterone, which has weak androgenic activity, was isolated by Butenandt and Dannenberg (11) in 1934. During the following year, testosterone was isolated from bull testes by David et al. (12). This hormone was shown to be 6 to 10 times as active as androsterone. 

Androgens are an important group of C19 steroids, principally comprised of testosterone (T) and its active metaboUte, 5a-dihydrotestosterone (DHT). In addition, androstenedione (AD) and dehydroepiandrosterone (DHEA) are usually classified as androgens, although their androgenic activity is low or neghgible. 

The major androgen or androgen precursor produced by the adrenal cortex is dehydroepiandrosterone (DHEA). Most 17-hydroxypregnenolone follows the glucocorticoid pathway, but a small fraction is subjected to oxidative fission and removal of the two-carbon side chain through the action of 17,20-lyase. The lyase activity is actually part of the same enzyme (P450cl7) that catalyzes 17tt-hydroxylation. This is therefore a dual function protein. The lyase activity is important in both the adrenals and... 

In most mammals, estrogens (female sex steroid hormones) are synthesized from cholesterol using the parent ring structure, cyclopentanoperhydrophenan-threne of the estrane series. The steroidogenic pathway includes the production of the androgenic precursors dehydroepiandrosterone and androstenedione, the latter of which is converted to testosterone, then to estradiol-17/i. This requires aromatization of these andogenic precursors by an aromatase enzyme complex. The major source of estrogen in postmenopausal women is the conversion of androstenedione to estrone by aromatase activity... 

As shown in Figure 5.3, pregnenolone (I) is oxidised to progesterone (II) and thence converted via 17a-hydroxyprogesterone (III) into testosterone (V). Testosterone is the most active of the naturally occurring androgens [9, 10]. Androstenedione (VI) and dehydroepiandrosterone (DHA) (IV) form less potent but quantitatively more significant secretion products. 

Placental aromatase deficiency. This results from a very low aromatizing activity of the placenta and thus fails to convert androgens derived from fetal dehydroepiandrosterone into estrogens (Shozu et al. 1991 MacGillivary et al. 1998). 

Fig. 19. Principal pathways in tbe transfer of androgen and eatri on conji tes between the amniotic cavity, fetus, placenta, and mother. (1) Possible alternatives (2) suggested glucuronidase activity- Ei estrone Kt estradiol estriol Ei S estrone sulfate Et-S estradiol sulfate Kj-S estriol sulfate Ei-Glu estrone glucuronide Ei-Glu estradiol glucuronide Ej-Glu estriol glucuronide Ej-S,Glu estriol-3-sulfale, IbiF ucuronide DIIA dehydroepiandrosterone I60-IIO-DHA l6a-hydroxydehydro-epiandrosterone DlIA-5 dehydroepiandrosterone sulfate I6a-I10-D1IA-S 16a-hy-droxydehydroepiandrasterone sulfate.

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