Characterisation of 11β-hydroxysteroid dehydrogenases in feline kidney and liver

Schipper, L.; Spee, Bart; Rothuizen, J.; Nijnanten, F. Woutersen-van; Fink‐Gremmels, Johanna

doi:10.1016/j.bbadis.2003.11.003

Cited by 14 publications

(10 citation statements)

References 47 publications

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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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“…11␤-HSD1 is also expressed in the kidney, primarily in proximal tubule cells (478,562,571,589,617,695), although any role remains largely unexplored. A: in normal weight health, 11␤-HSD1 acts largely as a reductase.…”

Section: E Kidneymentioning

confidence: 99%

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

Chapman

Holmes

Seckl

2013

Physiological Reviews

713

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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“…Therefore, we carried out a study aimed to provide comprehensive morphometric features and accurate measurements of the kidney structures in cat using design-based stereological procedures. Experimental studies on the kidney in the cat model have recently attracted particular interest due to similarities to human in the ontogeny of the kidneys and they are useful as translational models of human disease (Schipper et al, 2004;Ferguson et al, 2008;Finch et al, 2016;Dickerson et al, 2017). From the veterinary aspect, several disorders including chronic kidney disease (CKD; Brown et al, 2016;Martino-Costa et al, 2017), polycystic kidney disease (Nivy et al, 2015;Vucicevic et al, 2016), and renal amyloidosis (Godfrey and Day, 1998;Terio et al, 2008) have been reported to affect the kidney in cats.…”

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confidence: 99%

Cat Kidney Glomeruli and Tubules Evaluated by Design‐Based Stereology

Sadeghinezhad

Nyengaard

2019

The Anatomical Record

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Renal function is related to its structure and three‐dimensional structural parameters correlate better with the kidney function than two‐dimensional structural parameters. Stereology is the current gold‐standard technique for the morphometrical evaluation of kidney structures. This study describes morphometric features of the kidney of the cat using design‐based stereological techniques aimed to introduce the cat as a translational model in nephrology and provide basic findings for diagnosis and treatment of kidney diseases in this species. Left kidneys of four cats were included in the present study. The kidney volume, volume fraction of cortex and medulla, glomerular volume, glomerular mean volume, glomerular number, and proximal convoluted tubule (PCT) and distal convoluted tubule (DCT) length were estimated. The kidney volume was estimated to 11.4 ± 1.3 cm3. The volume fraction of cortex and medulla was 65.6 ± 2% and 34.2 ± 2%, respectively. The total number of glomeruli was estimated to be 186 ± 11 × 103 using the physical disector/fractionator method. The mean glomerular volume was estimated to be 1.54 ± 0.06 × 106 μm3 and the glomerular volume was covering 2.13 ± 0.34% of the whole kidney. The total length of PCT and DCT was estimated to be 2.26 ± 0.48 km and 505 ± 43 m, respectively. Our data might contribute to the knowledge of kidneys in mammals and provide a comparison with available data on human and other mammals. Anat Rec, 302:1846–1854, 2019. © 2019 American Association for Anatomy

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Characterisation of 11β-hydroxysteroid dehydrogenases in feline kidney and liver

Cited by 14 publications

References 47 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

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

Cat Kidney Glomeruli and Tubules Evaluated by Design‐Based Stereology

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