Interindividual variability in the expression and NNK carbonyl reductase activity of 11β-hydroxysteroid dehydrogenase 1 in human lung

Soldan, Michael; Nagel, G. A.; Losekam, M.; Ernst, Michael E.; Maser, Edmund

doi:10.1016/s0304-3835(99)00216-5

Cited by 34 publications

(25 citation statements)

References 25 publications

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“…Reports of HSD1 protein expression in adult human lung tissue have been confl icting. HSD1 protein has been detected in adult human lung tissue by some investigators, while others have been unable to confi rm these observations [83,[93][94][95]97] . The discrepancy in the ability to detect HSD1 protein in human lung may be related to the method of lung tissue preparation and/or the tissue tested.…”

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 94%

“…The discrepancy in the ability to detect HSD1 protein in human lung may be related to the method of lung tissue preparation and/or the tissue tested. HSD1 protein has been detected by immunoblot analysis of cultured adult lung fibroblasts and in microsome preparations of adult lung tissue [94,95] . However, HSD1 protein expression was undetectable by immunoblot analysis of total lung homogenate protein and immunohistochemical analysis of adult lung tissue [83,93,97] .…”

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 99%

“…To our knowledge, HSD1 protein expression in the human fetal lung has never been reported. However, HSD1 mRNA has been detected in adult human lung tissue and in cultured human lung fibroblasts [62,[94][95][96] . Reports of HSD1 protein expression in adult human lung tissue have been confl icting.…”

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 99%

“…Cultured adult and fetal lung fi broblasts seem to express high levels of HSD1 protein and enzymatic activity, which are not apparent in intact tissue [87,88,94] . Additionally, detection of HSD1 pro- tein in fresh adult lung required the use of relatively large amounts (100 g) of purifi ed microsomal protein [95] .…”

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 99%

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Glucocorticoid Metabolism in the Human Fetal Lung: Implications for Lung Development and the Pulmonary Surfactant System

et al. 2006

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It has been nearly 35 years since Liggins and Howie first reported the benefits of antenatal glucocorticoid (GC) treatment to promote the maturation of the human fetal lung, and nearly that long since Pasqualini and colleagues demonstrated that the human fetal lung actively metabolizes GCs. Since that time, our understanding of the effects of GCs on fetal lung maturation and pulmonary surfactant production has increased dramatically. Similarly, characterization of the enzymes involved in GC metabolism has greatly expanded our understanding of GC signaling in target tissues. In man, the biologically active GC (cortisol) and the biologically inactive GC (cortisone) are interconverted by the tissue-specific expression of the type 1 and type 2 11β-hydroxysteroid dehydrogenase enzymes (HSD1 and HSD2). Much of the research on GC metabolism in peripheral target tissues has focused on the role of HSD1 in amplifying the effects of GCs in liver and adipose tissue or on the role of HSD2 in blocking the effects of GCs in the kidney and placenta. In contrast, the role of GC metabolism in modulating the effects of GCs on fetal lung maturation and the pulmonary surfactant system in humans is less understood. The goal of this review article is to present a brief overview of the role of GCs in human fetal lung maturation and pulmonary surfactant production, and to familiarize the reader with the biochemistry of the metabolism of natural and synthetic GCs by the HSD enzymes. In addition, we will review data concerning the expression and activity of the HSD enzymes in the human fetal lung and contrast this to what is known about the HSD enzymes in the fetal rodent lung. Although rodents, rabbits, sheep, and several primates have been invaluable model systems for the study of fetal lung development, we have chosen to largely focus this review on human lung, since there are significant differences in GC metabolism between humans and other species.

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Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 94%

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 99%

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 99%

Section: Hsd Expression and Activity In The Developing Human Lungmentioning

confidence: 99%

See 2 more Smart Citations

Glucocorticoid Metabolism in the Human Fetal Lung: Implications for Lung Development and the Pulmonary Surfactant System

et al. 2006

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“…B) LUNG CANCER. Beyond glucocorticoid metabolism, 11␤-HSD1 also has carbonyl reductase activity, metabolizing key carcinogenic nitrosamines in tobacco smoke (657). Levels of the 11␤-HSD1 substrate 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its active products predict lung cancer risk (800).…”

Section: Lungmentioning

confidence: 99%

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

Chapman

Holmes

Seckl

2013

Physiological Reviews

698

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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The effect of water on the glass transition of human hair

et al. 2005

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The glass transition of human hair and its dependence on water content were determined by means of differential scanning calorimetry (DSC). The relationship between the data is suitably described by the Fox equation, yielding for human hair a glass transition temperature of T(g) = 144 degrees C, which is substantially lower than that for wool (174 degrees C). This effect is attributed to a higher fraction of hydrophobic proteins in the matrix of human hair, which acts as an internal plasticizer. The applicability of the Fox equation for hair as well as for wool implies that water is homogeneously distributed in alpha-keratins, despite their complex morphological, semicrystalline structure. To investigate this aspect, hair was rendered amorphous by thermal denaturation. For the amorphous hair neither the water content nor T(g) were changed compared to the native state. These results provide strong support for the theory of a quasi-homogeneous distribution of water within alpha-keratins.

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Interindividual variability in the expression and NNK carbonyl reductase activity of 11β-hydroxysteroid dehydrogenase 1 in human lung

Cited by 34 publications

References 25 publications

Glucocorticoid Metabolism in the Human Fetal Lung: Implications for Lung Development and the Pulmonary Surfactant System

Glucocorticoid Metabolism in the Human Fetal Lung: Implications for Lung Development and the Pulmonary Surfactant System

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

The effect of water on the glass transition of human hair

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