Erratum to ‘Ergosteroids II: biologically active metabolites and synthetic derivatives of dehydroepiandrosterone’ [Steroids 63 (1998) 158–165]

Lardy, Henry A.; Kneer, Nancy; Wei, Yuming; Partridge, Bruce; Marwah, Padma

doi:10.1016/s0039-128x(99)00002-1

Cited by 19 publications

(23 citation statements)

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“…DHEA may exert its pleiotropic effects following its conversion into several biologically-active metabolites, including 7α-hydroxy-DHEA (7α-OH-DHEA), 7β-hydroxy-DHEA (7β-OH-DHEA) and 7-oxo-DHEA [11,20]. For example, 7-oxo-DHEA, as well as 7α-and 7β-OH-DHEA, have been proposed to have biological actions in rodent and men [21][22][23][24] with higher effectiveness than the parent sterol DHEA [25,26].…”

Section: Discussionmentioning

confidence: 99%

Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: Nuclear and microsomal 11β-hydroxysteroid dehydrogenases

Robinzon

Prough

2005

Archives of Biochemistry and Biophysics

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The 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) activates glucocorticoids (GC) by reversibly converting 11-keto-GC to 11-hydroxy-GC, while 11βHSD2 and 11βHSD3 only catalyzes the reverse reaction. Recently, rat and human 11βHSDs were shown to interconvert 7α-and 7β-hydroxy-dehydroepiandrosterone (7α-or 7β-OH-DHEA) with 7-oxo-DHEA. We report that pig kidney microsomes (PKMc) and nuclei (PKN) oxidize 7α-OH-DHEA to 7-oxo-DHEA at higher rates with NAD + , than with NADP + . Corticosterone (CS), dehydrocoticosterone (DHC), 11α-and 11β-hydroxyprogesterone, and carbenoxolone completely inhibited these reactions, while 7-oxo-DHEA only inhibited the NAD + -dependent reaction. Conversely, CS oxidation was not inhibited by 7α-OH-DHEA or 7-oxo-DHEA. PKMc and PKN did not convert 7-oxo-DHEA to 7-OH-DHEA with either NADPH or NADH. Finally, PKN contained a high affinity, NADPH-dependent 11βHSD that reduces DHC to CS. The GC effects on interconversion of DHEA metabolites may have clinical significance, since DHEA and its 7-oxidized derivatives have been proposed for treatment of human autoimmune and inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: Nuclear and microsomal 11β-hydroxysteroid dehydrogenases

Robinzon

Prough

2005

Archives of Biochemistry and Biophysics

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“…Lardy et al (11,12) have reported two methods for the introduction of a hydroxyl group at the C-7 position of 3 ␤ -hydroxy-⌬ 5 structures. The first method is the stereoselective reduction of a 7-carbonyl group (11), and the second method is the oxidative debromination of 7-bromo compounds, which are produced by allylic bromination, in the presence of acetic acid and silver acetate (12). Because the latter method is more general, allows easier handling, and yields a mixture of 7-bromides with a 7 ␣ /7 ␤ ratio of ‫ف‬ 1:1, we used the allylic bromination procedure with dibromantin.…”

Section: Synthesis Of 3 ␤ 7 ␣ -Dihydroxy-5-cholenoic Acidmentioning

confidence: 99%

Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

Mano

Sato

Nagata

et al. 2004

Journal of Lipid Research

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We have previously demonstrated that the rat brain contains three unconjugated bile acids, and chenodeoxycholic acid (CDCA) is the most abundantly present in a tight protein binding form. The ratio of CDCA to the other acids in rat brain tissue was significantly higher than the ratio in the peripheral blood, indicating a contribution from either a specific uptake mechanism or a biosynthetic pathway for CDCA in rat brain. In this study, we have demonstrated the existence of an enzymatic activity that converts 3 ␤ -hydroxy-5-cholenoic acid into CDCA in rat brain tissue. To distinguish marked compounds from endogenous related compounds, 18 O-labeled 3 ␤ -hydroxy-5-cholenoic acid, 3 ␤ ,7 ␣ -dihydroxy-5-cholenoic acid, and 7 ␣ -hydroxy-3-oxo-4-cholenoic acid were synthesized as substrates for in vitro incubation studies. The results clearly suggest that 3 ␤ -hydroxy-5-cholenoic acid was converted to 3 ␤ ,7 ␣ -dihydroxy-5-cholenoic acid by microsomal enzymes. The 7 ␣ -hydroxy-3-oxo-4-cholenoic acid was produced from 3 ␤ ,7 ␣ -dihydroxy-5-cholenoic acid by the action of microsomal enzymes, and ⌬ 4 -3-oxo acid was converted to CDCA by cytosolic enzymes. These findings indicate the presence of an enzymatic activity that converts 3 ␤ -hydroxy-5-cholenoic acid into CDCA in rat brain tissue. Furthermore, this synthetic pathway for CDCA may relate to the function of 24 S -hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.

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“…We have used the induction of these two enzymes as an assay for DHEA-like activity of a large number of new steroids we have synthesized (38,39,(43)(44)(45)(46)(47). In a parallel study we have examined the metabolic conversion of DHEA to related steroid structures (48).…”

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confidence: 99%

Transformations of DHEA and its metabolites by rat liver

Lardy

Marwah

2002

Lipids

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Because dehydroepiandrosterone (DHEA) has a wide variety of weak beneficial effects in experimental animals and humans, we searched for metabolites of this steroid in the hope of finding more active compounds that might qualify for the title "steroid hormone." Incubation of DHEA with rat liver homogenate fortified with energy-yielding substrates resulted in rapid hydroxylation at the 7alpha-position of the molecule and subsequent conversion to other 7-oxygenated steroids in the sequence DHEA --> 7alpha-hydroxyDHEA --> 7-oxoDHEA --> 7beta-hydroxyDHEA, with branching to diols, triols, and sulfate esters. The ability of these metabolites to induce the formation of liver thermogenic enzyme activity increased from left to right in that sequence. A total of 25 different steroids were characterized, and at least six additional structures that are currently under study were produced from DHEA. 7-OxoDHEA is more effective than DHEA in enhancing memory performance in old mice and in reversing the amnesic effects of scopolamine.

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Erratum to ‘Ergosteroids II: biologically active metabolites and synthetic derivatives of dehydroepiandrosterone’ [Steroids 63 (1998) 158–165]

Cited by 19 publications

References 0 publications

Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: Nuclear and microsomal 11β-hydroxysteroid dehydrogenases

Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: Nuclear and microsomal 11β-hydroxysteroid dehydrogenases

Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

Transformations of DHEA and its metabolites by rat liver

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