Dehydroepiandrosterone, formation from

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 ... 

Formation of sulfates [328] is relatively reversible. This may be due to the fact that the metabolic clearance rate [318] of sulfates is relatively low [389] and their renal excretion inefficient [4]. The conversion of dehydroepiandrosterone sulfate in vivo to androsterone and etiocholanolone glucuronide was demonstrated by Lieberman and co-workers, who administered isotopically labeled dehydroepiandrosterone sulfate and isolated labeled androsterone and etiocholanolone from glucuronicase-hydrolyzed urine [303]. Since in another study by Lieberman [174], the transconjugation from dehydroepiandrosterone sulfate to dehydroepiandrosterone glucuronide without free dehydroepiandrosterone intermediate was declared to be improbable, in vivo equilibrium between dehydroepiandrosterone sulfate and dehydroepiandrosterone seems probable [303]. 

In addition to the usual suffixes and prefixes just discussed, a few special prefixes are usually used for the semi-trivial names of the compounds. Thus the prefix dehydro- is used to indicate the loss of two hydrogen atoms from adjacent carbon atoms with the formation of a double bond (e.g, dehydroepiandrosterone). The prefix dihydro- or tetrahydro- indicates the addition of two or four hydrogen atoms to the molecule, respectively, as in dihydrocortisol and tetrahydrocortisol. The replacement of a hydroxyl group by hydrogen (COH CH) is denoted by the prefix deoxy- (or desoxy- [e.g., 11-deoxycorticosterone]). 

DHEA (dehydroepiandrosterone) is another nonprescription antidepressant that has gone through cycles of popularity (Figure 6.2). DHEA, a steroid, is made from cholesterol in the adrenal gland and is part of the biochemical pathway in which hormones such as estrogen and testosterone are end-products. While its properties as a peripheral hormone are well characterized, less is known about DHEA s function in the brain. Media interest in DHEA arose when it was shown to prevent or slow memory loss in older populations. Further research showed that DHEA could influence neuronal function in the hippocampus, a region important for memory formation. However, several clinical studies showed mixed results when DHEA was used in... 

Admittedly only the axial and epimeric pairs can be reasonably easily separated from each other further subdivision is difficult and more is said about this in connection with the urinary 17-ketosteroids. Even the 3j5,6a-isomer (epiandrosterone) cannot be separated from the important J ,3iS-compound (dehydroepiandrosterone) using normal TLC. As mentioned in the preceding section, complex formation on silver nitrate-containing layers helps in this instance. Many synthetic Cig -steroids contain a 17a-alkyl as well as the 17j8-hydroxyl group the former reduces the polarity in the order — CH3, — CgHg, — CH=CH2 equals — CsCH, — C3H7. 

It is interesting to note that in spite of a very large concentration of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the umbilical artery, no 16af-hydroxylation takes plaa in placental tissue (Jackanicz and Diczfalusy, 1968) consequently, the formation of placental estriol re.sults mainly from fetal precursors. 

In the placental tissue, there is an extensive formation of androstenedione from dehydroepiandrosterone, which is obtained mostly by the hydrolysis of dehydroepiandrosterone sulfate, which is biosynthesized principally in the fetal compartment. On the other hand, as was indicated before (Section 111, B, 1, a), in the placental compartment very few if any Cw steroids arc formed from Cm steroids by side-chain cleavage (Warren and Cheatum, 1964 Jaffe et al., 1965). Also, since androstenedione is not a good substrate for 17d-rcductasc, it can be assumed that most of the placental t( Stosterone originates from fetal androstenediol (Uell Acqua et al., 1966, 1967a,b). It is interesting to note that thi.s latter steroid is a normal const.ituent of cord blood (Kberlein, 1965). 

The formation of estrone and estradiol in placental tissues come.s principally from fetal dehj droepiandrosterone sulfate. In 1955, Migeon et al. obsei"ved that more dehydroepiandrosterone is present in the umbilical cord blood than in maternal plasma. These results have been confirmed and since, as indicated previously (Section HI, F, 1, a), the concentration of dehydroepiandrosterone sulfate is higher in the umbilical artery than in the umbilical vein, the fetal compartment must secrete dehydroepiandrosterone sulfatt to the placental compartment. 

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