DHEA sulfate

Numerous deuterated neuroactive steroids are now available from commercial sources (Cambridge Isotope Laboratories Inc, Andover, MA C/D/N/Isotopes Inc., Pointe-Claire, Quebec, Canada Steraloids Inc., Newport, RI). The most useful of these deuterated steroids are those containing two or more nonexchangeable deuteriums, such as the [3a, 7,7- H3]-analogs of DHEA sulfate (O Figure 7-4c) and PREG... 

DHEA sulfate is more suited to measurement by negative-ion ES-MS, as demonstrated in an early study by Shackleton et al. [86]. 

Guo and co-workers [24,25] have spearheaded the development of MS/MS serum steroid profiles. Their most recent report describes profiling in 11 min of 12 steroids in 200 pi serum with minimal work-up, comprising acetonitrile protein precipitation. The steroids analyzed were as follows DHEA sulfate, DHEA, aldosterone, cortisol, corticosterone, 11-deoxycortisol, androstenedione, estradiol, testosterone, 17-hy-droxyprogesterone, progesterone, and 25-hydroxyvitamin D3. Stable-isotope-labeled internal standards were incorporated for each steroid. An API-5000 instrument was used with the APPI source in positive-ion mode, with the exception of aldosterone, which had greater sensitivity in negative-ion mode. Separation was carried out on a C8 column, which allowed more rapid separation than the more commonly utilized C18. The MRM transitions utilized are shown in Table 5.3.1. The lower level of sensitivity was between 1.5 and 10 pg/ml, dependent on the steroid. The authors were exhaustive in addressing issues of accuracy, recovery (90-110%) and reproducibility (< 12.2% for same-day and between-day). 

Dehydroepiandrosterone (DHEA) is a precursor hormone secreted by the adrenal cortex and to a lesser extent by the central nervous system (Chapter 40 The Gonadal Hormones Inhibitors). It is readily converted to androstenedione, testosterone, and androsterone. In peripheral tissues, aromatase converts DHEA to estradiol. In the plasma, DHEA is converted to DHEA sulfate (DHEAS). 

The adrenal glands play an important role in pubertal development. Termed adrenarche, the maturation of a prominent zona reticularis, the innermost layer of the cortex, begins around age six to eight in girls, resulting in increased secretion of the adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (Beckman Feuston, 2003). The rise in these hormones leads to the development of pubic and axillary hair. Recent evidence suggests... 

Decreased DHEA production has also been linked to increased IL-6 levels in mice. Here, the administration of DHEA sulfate to old mice resulted in decreased... 

Straub, R. H., Konecna, L., Hrach, S., Rothe, G., Kreutz, M., etal., Serum dehydroepiandros-terone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro Possible link between endocrinosenescence and immunosenescence. J. Clin. Endocrinol. Metab. 83, 2012-2017 (1998). 

K. Mitamura, Y. Nagaoka, K. Shimada, S. Honma, M. Namiki, E. Koh, A. Mizokami, Simultaneous determination of androstenediol 3-sulfate and DHEA sulfate in human serum using isotope diluted LC-ESI-MS, J. Chromatogr. B, 796 (2003) 121. 

DHEA sulfate (DHEAS) Cortex (zona reticularis) 200,000 100... 

Liu et al. (2003) focused their method paper on the instrumental set-up for on-line capillary LC coupled with MS-MS via a low flow-rate interface, hoping that miniaturization would improve sensitivity for many biomedical applications. The system design and perfonnance were tested on DHEA sulfate and pregnenolone sulfate quantitation from 5 pL of plasma from one male volunteer. Sample preparation was simple - addition of aqueous methanol and of the deuterated analog internal standards, protein precipitation, supernatant filtration through a Cig bed, evaporation and reconstitution in 100 pL of mobile phase, of which 20 pL were injected for LC-MS-MS analysis. The DHEA sulfate concentration found was in agreement with literature values based on GC-MS and LC-MS studies. 

Another agent that has undergone Phase III clinical trials for SCI is GMl ganglioside. Since high-dose methylprednisolone had become widely accepted for treatment of SCI, GMl was administered only after the completion of the 24 hr methylprednisolone dosing protocol. The results indicated that GMl did not provide greater functional improvement compared to methylprednisolone alone (Hall and Springer, 2004). The neurosteroid, DHEA sulfate offered... 

Takayanagi, R., K. Goto, S. Suzuki, S. Tanaka, S. Shimoda, and H. Nawata (2002). Dehy-droepiandrosterone (DHEA) as a possible source for estrogen formation in bone cells Correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1,25-dihydroxyvitamin Dj in human osteoblasts. Mech. Ageing Dev. 123, 1107-1114. 

Nature Dehydroepiandrosterone (DHEA), derived mainly from the adrenal cortex, is an androgen precursor and in peripheral tissues is converted by aromatase to estradiol, fit the plasma, DHEA is converted to DHEA sulfate (DHEAS). No specific physiologic function has been defined for DHEA or DHEAS. However, DHEA levels decrease during aging and possibly in some disease states, including advanced AIDS, diabetes, and systemic lupus erythematosus (in women). 

OATP1A2 (OATP-A) Ajmalin, DHEA-Sulfate, 17(1-Estradiol, Estrone, Microcystin, N-Methyl-quinidine, Ouabain, Prostaglandin E2, Rocuronium, Thyroxin (T4), Triiodothyronine (T3)... 

One more item to consider is that the dysfunctional HPA axis can lead to the decrease in plasma levels of DHEA and DHEA sulfate, DHEAS. Such conditions are associated with the above described mental states. Conversely, increased levels of DHEA, by antagonizing glucocorticoid s antiimmunosuppressivo properties, provides the body with protection against viral or infection-mediated degenerative diseases. In general, high levels of cortisol and depressed serum concentrations of DHEAS are associated with serious illnesses. 

Cho, S.-H. Jung, B.H. Lee W.-Y. Chung, B.C. Rapid column-switching liquid chromatography/mass spectro-metric assay for DHEA-sulfate in the plasma of patients with Alzheimer s disease. Biomed. Chromatogr. 2006, 20, 1093 1097. 

CYB5A, yielding dehydroepiandrosterone (DHEA), which enters the circulation as DHEA sulfate (DHEAS), a substrate for P450 3A7 in the fetal liver below dashed line in box). In the plaeenta, steroid sulfatase removes the sulfate from 16a-hydroxyDHEAS, and 3PHSD1 oxidizes and isomerizes 16a-hydroxyDHEA, to yield 16a-hydroxyandrostenedione. Placental P450aro and 17PHSD1 catalyze the final transformations to 16a-hydroxyestrone and estriol, respectively. 

Estimation of Dehydroepiandrosterone [DHEA] Sulfate in Human Serum by Gas-Liquid Chromatography Anal. Biochem. 14(3) 337-346 (1966) CA 64 13049c... 

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