Dehydroepiandrosterone 7α-hydroxylation in human tissues: Possible interference with type 1 11β-hydroxysteroid dehydrogenase-mediated processes

Hennebert, Olivier; Chalbot, Sonia; Alran, S.; Morfin, Robert

doi:10.1016/j.jsbmb.2007.03.026

Cited by 77 publications

(58 citation statements)

References 42 publications

(48 reference statements)

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“…11␤-HSD1 is widely expressed in human and mouse epidermis and dermis (276,699), but is highest in keratinocytes in the suprabasal area of the epidermis and dermal fibroblasts where it is a reductase (121). Keratinocyte 11␤-HSD1 increases with differentiation (699), parallelling the enzyme's pattern during differentiation of preadipocytes (510).…”

Section: Skinmentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

703

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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Section: Skinmentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

703

601

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“…This finding was extended to the native enzyme present in human skin tissue homogenates 11 . In the presence of NADPH, the recombinant human 11β-HSD1 reduced 7-oxo-DHEA into 7β-hydroxy-DHEA in preference to 7α-hydroxy-DHEA as indicated by a higher V max /K M ratio ( Table 2) 10 .…”

Section: Discussionmentioning

confidence: 69%

“…Origin of 7β-hydroxy-DHEA and 7β-hydroxy-EpiA was investigated in several human models 8,9 . Use of a yeast-expressed recombinant human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) helped to demonstrate that 7β-hydroxy-DHEA derived from 7α-hydroxy-DHEA through a 7-oxo-DHEA intermediate 10,11 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Steroid substrate-induced epimerase mechanism in the active site of the human 11&946;-hydroxysteroid dehydrogenase type 1

et al. 2008

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“…Эти соединения участвуют в регуляции процесса воспаления [29]. В ряде исследований отмечено сопряженное с воспалением изменение обмена холестерина [30][31][32], что может отразиться на образовании изопрена [33] и ряда других соединений (дегидроэпиандростерона, дегидроэпиандростерон-сульфата, 17-гидроксипрогестерона, андростендиона [34], 7альфа-гидроксидегидроэпиандростерона [35,36] Итак, анализ системных и внутриклеточных процессов свидетельствует о том, что при аутоиммунных патологиях можно ожидать изменений в концентрации таких ЛОС, как ацетон и изопрен, которые выделяются в составе выдыхаемого воздуха. Для проверки данного предположения были исследованы пациенты, проходившие стандартный курс лечения в Институте клинической иммунологии СО РАМН (Новосибирск).…”

Section: летучие органические соединения (лос) при аутоиммунной патолunclassified

PPROMEDIA – Database of Chemical Substances the Potential Biomarkers of Diseases with the Meaning in Noninvasive Diagnostics

Saik¹

2011

Math.Biol.Bioinf.

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Dehydroepiandrosterone 7α-hydroxylation in human tissues: Possible interference with type 1 11β-hydroxysteroid dehydrogenase-mediated processes

Cited by 77 publications

References 42 publications

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Steroid substrate-induced epimerase mechanism in the active site of the human 11&946;-hydroxysteroid dehydrogenase type 1

PPROMEDIA – Database of Chemical Substances the Potential Biomarkers of Diseases with the Meaning in Noninvasive Diagnostics

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