Dehydroepiandrosterone, production

D3. Danenberg, H. D., Alpert, G., Lustig, S., and Ben-Nathan, D., Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production. Antimicrob. Agents Chemother. 36,2275-2279 (1992). 

The byproduct sitosterol was for many years quite useless due to the lack of a chemical point of attack on the side chain that would permit its removal. Extensive efforts on the part of many laboratories eventually led to the discovery of a pseudomonas microbe that efficiently effected that transformation. Fermentation of (4-1) digests the entire aliphatic side chain at 17 to afford a mixture of 17-keto products including dehydroepiandrosterone (4-2) [4]. 

In all species, metabolism of testosterone leads to its biological deactivation. In sheep and cattle, this biological deactivation leads mainly to formation of epitestosterone, whereas in nonruminants it leads to androsterone, etiocholano-lone, and dehydroepiandrosterone (7-9). Residues of endogenous testosterone are usually highest in the kidneys of animals such as heifers witli a low testosterone production rate, and highest in fat of animals such as bulls, with a high production rate. 

The medical use of botanicals in their natural and unprocessed form undoubtedly began when the first intelligent animals noticed that certain food plants altered particular body functions. Much information exists about the historical use and effectiveness of botanical products. Unfortunately, the quality of this information is extremely variable. One of the most complete compendiums of clinical recommendations regarding the use of botanicals is the Report of the German Commission E (a committee that sets standards for herbal medications in that country Blumenthal, 2000). Interest in the endocrine effects and possible nutritional benefits of certain purified chemicals such as dehydroepiandrosterone. melatonin, high-dose vitamins, and minerals has led to a parallel development of consumer demand for such substances. These substances, together with the botanicals, constitute a substantial source of profits for those who exploit the concept of "alternative medicine."... 

Overall, other adrenal androgens also show a progressive decrease in urinary excretion in both men and women. Thus, the mean 17-ketosteroid urine levels of elderly people are about 50% of those in young adults. This is primarily secondary to decreased dehydroepiandrosterone (DHEA) and androsterone production. In men, about one-third of the daily 17-ketosteroids are of testicular origen, the remainder being mainly from the adrenals. Androstenedione is a prehormone for testosterone. 

The liver is the most important area for (he production of cholesterol and bile acids. The ovaries are the most important sources of estrogen and progesterone (progesterone is produced in the corpus luteum of the ovary). The testes are the major site of androgen production, testosterone especially. The adrenal cortex produces the mineralocorticoids and glucocorticoids, and the androgens dehydroepiandrosterone and androstenedione. 

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]. 

I) Consider three structurally similar Cis steroids —testosterone, an-drostenedione, and dehydroepiandrosterone. Each of these compounds is secreted into the blood stream by glands, and after provoking its biochemical effect, is metabolized and excreted. If the only source of the plasma pool were provided by the glandular secretion of the hormone, then the secretion rate would be used to calculate the plasma concentration. However, the picture in the case of the three Ci steroids is complicated by the fact that the three compounds are peripherally interconvertible. Since both glandular secretion and peripheral conversion of precursors contribute to the plasma pool, the production rate is used to... 

It has been shown that hormones are not exclusive products of the glands but are also formed in metabolizing organs. These hormones, however, contrary to the classical hormones, are not secreted into the blood. It has been established that testosterone formed in the liver from androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate does not enter the blood [305,323,388]. It has also been established that secreted and metabolically produced testosterone do not have the same metabolism [169, 311]. 

Furthermore Tait and co-workers [322] pointed out the marked difference in the urinary and blood production rates of testosterone obtained in women after injection of radioactive testosterone. He concluded that steroids produced from dehydroepiandrosterone contribute little to the blood production rate of androstenedione and testosterone in normal subjects [403]. According to Tait [324], all the blood production rate of androstenedione in the female and testosterone in the male is due to the same secreted steroid, while the blood production rate of testosterone in the female and androstenedione in the male is due about one-half to the same secreted steroid and one-half to converted precursor. The normal male secretes a ratio of testosterone to androstenedione of about 10 1 and the normal female secretes a ratio of androstenedione to testosterone of about 25 1. 

Thompson, R.D. Carlson, M. Liquid chromatographic determination of dehydroepiandrosterone (DHEA) in dietary supplement products. J. AOAC Int. 2000, 83 (4), 847-857. 

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... 

Fig. 1 Human steroidogenic pathway from cholesterol to adrenal or gonadal steroid products. CYP cytochrome P450 enzyme, ftSfthydroxysteroid dehydrogenase, DHEA dehydroepiandrosterone, Oft hydroxy, arom aromatase...

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... 

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