Dehydroepiandrosterone

Dehydroepiandrosterone added in vitro to alveolar macrophages lavaged from 11 non-smoking asbestos workers significantly reduced superoxide anion release (Rom and Harkin 1991). 

Pentoxifylhne (1 mM) stimulated the rate of rabbit alveolar macrophage spreading on glass covers-hps more than twofold (Wang et al. 1996). It reduced superoxide generation induced by phorbol-myristate-acetate by 50 %. Production of TNF-a induced by lipopolysaccharide was suppressed 85%. 

---

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

The reaction of ethyl a-bromoacetate with 17-keto steroids such as estrone methyl ether or dehydroepiandrosterone acetate " under standard Reformatsky conditions is stereospecific, producing the 17 -ol in up to 80% yields. Ethyl a-bromopropionate reacts similarly but the yields are somewhat lower. 

The 17,20-glycol grouping (with or without an additional C-21 alcohol) can be cleaved to the 17-ketone by any of the four reagents. However, the presence of a 20-ketone has a marked influence on reactivity. Thus, 17a-hydroxy-20-ketones lacking additional oxygenation at C-21 are readily cleaved only by chromium trioxide. A recent report,however, claims that 17a-hydroxypregnenolone 3-acetate can be quantitatively cleaved to dehydroepiandrosterone acetate using lead tetraacetate in an aprotic solvent... 

Hydrolysis of the acetate (71) followed by Oppenauer oxidation gives B-norcholest-4-en-3-one in high yield. An analogous reaction sequence can be used to prepare B-norprogesterone and derivatives of B-nortestosterone from pregnenolone acetate and dehydroepiandrosterone acetate, respectively."" ... 

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

Preparation of the newest of these, spirorenone (61), starts by 7-hydroxylation of dehydroepiandrosterone derivative Though this transformation has also been... 

Neurosteroids Progesterone, dexamethasone, dehydroepiandrosterone Study findings have been negative. 

DHEA Dehydroepiandrosterone SHBG Sex hormone-binding globulin... 

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... 

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.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate, its sulphated derivative... 

The researeh on dehydroepiandrosterone (DHEA) is limited beeause of the laek of radiolabeled metabolites. Robinzon et al. [126] showed that, using pig liver mierosomes, the radiolabeled metabolites of DHEA can be prepared in stable, pure form for bioehemical smdies. They utilized pig liver microsomal (PLM) fractions to prepare pH]-labeled 7a-hydroxy-DHEA (7a-OH-DHEA), 7[3-hydroxy-DHEA (7P-OH-DHEA), and 7-oxo-DHEA substrates from 50 pM [1,2,6,7-3H]DHEA. The metabolites were separated by silica gel PLC plates using ethyl aeetate-hexane-gla-eial aeetic acid (18 8 , v/v) as the mobile phase, extracted with ethyl aeetate, and dried under a stream of nitrogen. The purity of markers was determined with the use of TLC and GC/MS. 

The zona reticularis produces the androgens androstene-dione, dehydroepiandrosterone (DHEA), and the sulfated form of dehydroepiandrosterone (DHEA-S). Only small amounts of testosterone and estrogen are produced in the adrenal glands. Androstenedione and DHEA are converted in the periphery, largely to testosterone and estrogen. 

---