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Rodion Belousov
Rodion Belousov

7 Hydroxy Dhea Buy !!TOP!!



7α-Hydroxydehydroepiandrosterone (7α-hydroxy-DHEA; 7α-OH-DHEA), also known as 3β,7α-dihydroxyandrost-5-ene-17-one, is an endogenous, naturally occurring steroid and a major metabolite of dehydroepiandrosterone (DHEA) that is formed by CYP7B1 (steroid 7α-hydroxylase) in tissues such as the prostate gland and by CYP3A4 in the liver.[1][2] The major metabolic pathway of DHEA outside the liver is via 7-hydroxylation into 7α-OH-DHEA and 7β-OH-DHEA.[3] 7α-OH-DHEA has weak estrogenic activity, selectively activating the estrogen receptor ERβ.[2] In addition, 7α-OH-DHEA may be responsible for the known antiglucocorticoid effects of DHEA.[4][5]




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7-Hydroxylated metabolites of dehydroepiandrosterone (DHEA) are believed to be responsible for at least some immunomodulatory and antiglucocorticoid effects of DHEA and hence are considered candidates for hormone replacement therapy. Our experiments in vitro brought the evidence that 3beta, 7beta-dihydroxy-5-androsten-3-one (7beta-OH-DHEA), but not DHEA and its 7alpha-hydroxyisomer, could counteract the immunosuppressive effect of dexamethasone on the formation of plaques in culture of murine spleen lymphocytes. In another experiment, DHEA and after a 3-weeks pause 3beta-hydroxy-5-androstene-7,17-dione (7-oxo-DHEA) were applied transdermally to 6 male volunteers on 5 consecutive days. Blood levels of DHEA, its 7-hydroxylated metabolites, and in the first case also dehydroepiandrosterone sulphate (DHEAS), were measured before, during and one day after the end of treatment. Application of DHEA increased significantly not only DHEA and DHEAS, but also its both 7-hydroxyisomers. Application of 7-oxo-DHEA also led to a significant increase of both 7-hydroxyisomers of DHEA, with 7beta-OH-DHEA being the preferred metabolite the concentration of which was increased more than three times.


The neuroprotective action of dehydroepiandrosterone (DHEA) in the absence of a known specific receptor has been attributed to its metabolism by different cell types in the brain to various steroids, with a preference to its 7-hydroxylated products. The E(t)C cerebellar granule cell line converts DHEA almost exclusively to 7α-hydroxy-DHEA (7α-OH-DHEA). It has been postulated that DHEA's 7-OH and 7-oxo metabolites can decrease glucocorticoid levels by an interactive mechanism involving 11β-hydroxysteroid dehydrogenase (11β-HSD). In order to study the relationship of 7-hydroxylation of DHEA and glucocorticoid metabolism in intact brain cells, we examined whether E(t)C cerebellar neurons, which are avid producers of 7α-OH-DHEA, could also metabolize glucocorticoids. We report that E(t)C neuronal cells exhibit 11β-HSD1 reductase activity, and are able to convert 11-dehydrocorticosterone into corticosterone, whereas they do not demonstrate 11β-HSD2 dehydrogenase activity. Consequently, E(t)C cells incubated with DHEA did not yield 7-oxo- or 7β-OH-DHEA. Our findings are supported by the reductive environment of E(t)C cells through expression of hexose-6-phosphate dehydrogenase (H6PDH), which fosters 11β-HSD1 reductase activity. To further explore the role of 7α-OH-DHEA in E(t)C neuronal cells, we examined the effect of preventing its formation using the CYP450 inhibitor ketoconazole. Treatment of the cells with this drug decreased the yield of 7α-OH-DHEA by about 75% without the formation of alternate DHEA metabolites, and had minimal effects on glucocorticoid conversion. Likewise, elevated levels of corticosterone, the product of 11β-HSD1, had no effect on the metabolic profile of DHEA. This study shows that in a single population of whole-cells, with a highly reductive environment, 7α-OH-DHEA is unable to block the reducing activity of 11β-HSD1, and that 7-hydroxylation of DHEA does not interfere with the activation of glucocorticoids. Our investigation on the metabolism of DHEA in E(t)C neuronal cells suggest that other alternate mechanisms must be at play to explain the in vivo anti-glucocorticoid properties of DHEA and its 7-OH-metabolites.


7β-Hydroxydehydroepiandrosterone (7β-hydroxy-DHEA; 7β-OH-DHEA), also known as 3β,7β-dihydroxyandrost-5-ene-17-one, is an endogenous, naturally occurring steroid and a metabolite of dehydroepiandrosterone (DHEA). The major metabolic pathway of DHEA outside the liver is via 7-hydroxylation into 7α-OH-DHEA and 7β-OH-DHEA.[1] 7β-OH-DHEA has weak antiestrogenic activity, selectively antagonizing the estrogen receptor ERβ.[2]


Glucocorticoids have successfully been used in the treatment of rheumatoid arthritis. Data suggest that 7α-hydroxy-dehydroepiandrosterone (7α-OH-DHEA), an immunostimulating metabolite of dehydroepiandrosterone, can block glucocorticoid-induced immune suppression. Formation of 7α-OH-DHEA is catalyzed by activity of cytochrome p450 enzyme 7b (Cyp7b). Recently, we reported that tumour necrosis factor (TNF)-α, IL-1α, IL-1β and IL-17 enhance Cyp7b mRNA expression and induce a concomitant increase in the formation of 7α-OH-DHEA by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis patients. The aim of this study was to elucidate which signal transduction pathway is involved in the TNF-α-mediated induction of Cyp7b activity in FLS. We studied the effects of inhibitors of different signal transduction pathways on Cyp7b activity in FLS by measuring Cyp7b mRNA expression using reverse transcription PCR and by measuring the formation of 7α-OH-DHEA. We applied SN50, an inhibitor of nuclear translocation of transcription factors (i.e. activator protein-1 [AP-1] and nuclear factor-κB [NF-κB]); PSI, a proteasome inhibitor that prevents IκB degradation and thereby NF-κB release; SP600125, a c-Jun N-terminal kinase (JNK) inhibitor; and the mitogen-activated protein kinase inhibitors PD98059 (extracellular signal-regulated kinase) and SB203580 (p38). Cyp7b is constitutively expressed in RA FLS and can be activated in response to TNF-α. SN50 and PSI prevented the TNF-α-induced increase in Cyp7b activity, whereas the mitogen-activated protein kinase inhibitors PD98059 and SB203580 had no effect. In addition, inhibition of Cyp7b mRNA expression and activity was observed with SN50, PSI and SP600125, suggesting that NF-κB and AP-1 induce Cyp7b transcription. These findings suggest that NF-κB and AP-1 are involved in the TNF-α-enhanced formation of the dehydroepiandrosterone metabolite 7α-OH-DHEA. Our results are in accordance with presence of AP-1 and NF-κB binding sites in the Cyp7b promoter.


Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of fibroblast-like synoviocytes (FLS), which is regarded to be important in cartilage and bone erosion [1]. Steroids such as dehydroepiandrosterone (DHEA), glucocorticoids, androgens and oestrogens have been shown to modulate the disease process in RA [2]. Several authors have suggested that the natural, abundantly present steroid DHEA may have immunostimulating effects [3, 4]. Further data indicate that the 7α-hydroxy-dehydroepiandrosterone (7α-OH-DHEA) metabolite of DHEA, rather than DHEA itself, is responsible for these immunostimulating effects [5, 6]. In several studies 7α-OH-DHEA was found to stimulate the immune system both in vitro and in vivo, and it has been suggested that 7α-OH-DHEA acts as an antiglucocorticoid [6, 7].


Beauveria bassiana is an entomopathogenic fungus used as a biological control agent. It is a well-known biocatalyst for the transformation of steroid compounds. Hydroxylations at the 7α or 11α position and oxidation to D-homo lactones are described in the literature. In our study, we examined the diversity of metabolism of five different B. bassiana strains and compared them to already known pathways. According to the literature, 7α and 11α-hydroxy derivatives as well as 3β,11α-dihydroxy-17a-oxa-D-homo-androst-5-en-17-one have been observed. Here we describe new DHEA metabolic pathways and two products not described before: 3β-hydroxy-17a-oxa-D-homo-androst-5-en-7,17-dione and 3β,11α-dihydroxyandrost-5-en-7,17-dione. We also used for the first time another species from this genus, Beauveria caledonica, for steroid transformation. DHEA was hydroxylated at the 7α, 7β and 11α positions and then reactions of oxidation and reduction leading to 3β,11α-dihydroxyandrost-5-en-7,17-dione were observed. All tested strains from the Beauveria genus effectively transformed the steroid substrate using several different enzymes, resulting in cascade transformation.


Among steroid hormones, dehydroepiandrosterone (DHEA) is the most abundant adrenal hormone circulating in human blood. DHEA is synthesised from cholesterol mainly in adrenal glands but also in testes, ovaries and brain1. It is metabolised by bone, muscle, breast, skin and adipose tissue as well as brain, intestine and liver1,2. DHEA is transformed further, to biologically active androgens and estrogens, but its hydroxy derivatives play a significant role2,3. Oxygenated derivatives can affect memory and cognitive functions4,5,6, rheumatologic arthritis7,8, colitis9,10,11, thermogenesis12,13, the immune response and autoimmune diseases14,15,16,17. At this stage of knowledge, the most promising as drugs are 7α- and 7β-hydroxy-DHEA, the main products of oxidation. They are formed from DHEA in liver, skin and brain by CYP7B1 (7α-hydroxylase) and by interconversion via 7-oxo-DHEA to 7β-hydroxy-DHEA by 11β-hydroxysteroid dehydrogenase type I (11β-HSD1)2,18. The level of DHEA in the cerebrospinal fluid is higher than the blood level and it has neuroprotective activities. Lowered expression of CYP7B1 in the human brain was observed in Alzheimer disease2,19. As mentioned above, oxygenated derivatives of DHEA may play an important role in many functions and diseases.


Biotransformation of steroid compounds is an easy method of obtaining hydroxy derivatives at inactivated positions. Although microbial strains capable of hydroxylating at any steroid position (except C4, 10 and 13) are known, there is still a need to screen for a new organism than can perform the desired transformations20. Selecting species for metabolism testing should not be entirely based on literature data. Fusarium acuminatum KCh S1 and Mucor hiemalis KCh W2 provide hydroxylation only at the 7α position, similar to Aspergillus versicolor KCh TJ1, while Penicillium commune KCh W7 and Penicillium chrysogenum KCh S4 do not hydroxylate DHEA at C7, in contrast to literature data21,22. However, every strain should be treated individually. All 13 strains of Isaria farinosa used in our previous studies provide the same reaction for DHEA, while this study presents five different transformation pathways for Beauveria bassiana strains23. 041b061a72


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