The 11β hydroxysteroid dehydrogenase 2 exists as an inactive dimer

Gómez-Sánchez, Elise P.; Ganjam, Venkataseshu K.; Chen, Yuan Jian; Liu, Ying; Clark, Suzanne A; Gómez-Sánchez, Celso E.

doi:10.1016/s0039-128x(01)00119-2

Cited by 41 publications

(46 citation statements)

References 24 publications

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“…At the end of each experiment the rats (275-325 g; male; Sprague Dawley Harlan, Indianapolis, IN) were anesthetized with pentobarbital (50 mg/kg) and perfused transcardially with isotonic saline, followed by 4% paraformaldehyde in 0.1 M sodium phosphate buffer, pH 7.4. Double-immunofluorescence staining was performed by using a sheep antibody raised against HSD2 (1:40,000; Chemicon, Temecula, CA) (Gomez-Sanchez et al, 2001) combined with a rabbit antibody that specifically labels MR (1:5000) (Ito et al, 2000) or c-Fos (1: 10,000; c-Fos Ab-5 from Oncogene, Cambridge, MA).…”

Section: Methodsmentioning

confidence: 99%

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

Geerling¹,

Engeland²,

Kawata³

et al. 2006

J. Neurosci.

135

187

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Sodium appetite can be enhanced by the adrenal steroid aldosterone via an unknown brain mechanism. A novel group of neurons in the nucleus tractus solitarius expresses the enzyme 11-␤-hydroxysteroid dehydrogenase type 2, which makes them selectively responsive to aldosterone. Their activation parallels sodium appetite in different paradigms of salt loss even in the absence of aldosterone. These unique aldosterone target neurons may represent a previously unrecognized central convergence point at which hormonal and neural signals can be integrated to drive sodium appetite.

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Section: Methodsmentioning

confidence: 99%

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

Geerling¹,

Engeland²,

Kawata³

et al. 2006

J. Neurosci.

135

187

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“…It is interesting that catalytic activity of both mutant enzymes was completely abolished upon cell lysis, indicating a similar inhibitory mechanism. Two earlier studies found higher 11␤-HSD2 activity in the presence of the reducing agent dithiothreitol in cell lysates (23,24 …”

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confidence: 94%

Impaired Protein Stability of 11β-Hydroxysteroid Dehydrogenase Type 2

Atanasov

Ignatova

Nashev

et al. 2007

Journal of the American Society of Nephrology

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Apparent mineralocorticoid excess (AME) is a severe form of hypertension that is caused by impaired activity of 11␤-hydroxysteroid dehydrogenase type 2 (11␤-HSD2), which converts biologically active cortisol into inactive cortisone. Mutations in HSD11B2 result in cortisol-induced activation of mineralocorticoid receptors and cause hypertension with hypokalemia, metabolic alkalosis, and suppressed circulating renin and aldosterone concentrations. This study uncovered the first patient with AME who was described in the literature, identified the genetic defect in HSD11B2, and provided evidence for a novel mechanism of reduced 11␤-HSD2 activity. This study identified a cluster of amino acids (335 to 339) in the C-terminus of 11␤-HSD2 that are essential for protein stability. His and wild-type 11␤-HSD2 occurs through the proteasome pathway. Therefore, impaired 11␤-HSD2 protein stability rather than reduced gene expression or loss of catalytic activity seems to be responsible for the development of hypertension in some individuals with AME.

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“…Both message and protein for 11b-HSD1 were reduced to very low levels by estradiol in the rat kidney, whereas those for 11b-HSD2 were greatly increased. Notwithstanding, in vivo activity, as measured by the ratio of urinary corticosterone to 11-dehydrocorticosterone, was not different between kidneys of control and estrogentreated rats, apparently owing to the formation of inactive dimers (Gomez-Sanchez et al 2001, suggesting that 11b-HSD2 activity may be regulated in vivo by dimer formation. Whether dimerization occurs only in those cells in which the estrogen-induced increase in 11b-HSD2 is not adaptive is not known.…”

Section: Discussionmentioning

confidence: 84%

“…MR and both 11b-HSD enzymes were expressed in the ovarian stroma comprising various cell types, including hilar cells that produce androgens and macrophages that participate in the dissolution of old corpora lutea and produce cytokines important for the regulation of steroidogenesis in the ovary (Bornstein et al 2004). Changes in 11b-HSD1 and -2 message and even protein expression do not necessarily translate into al- tered enzyme activity (Gomez-Sanchez et al 2001. Both message and protein for 11b-HSD1 were reduced to very low levels by estradiol in the rat kidney, whereas those for 11b-HSD2 were greatly increased.…”

Section: Discussionmentioning

confidence: 95%

“…Microsomes comprising primarily ER and plasma membrane were isolated by differential centrifugation as we have done before (Morita et al 1996), then solubilized using Laemmli buffer (Laemmli 1970) and run in a 12% PAGE (11b-HSD) or 7.5% PAGE (H6PDH), transferred by semidry blot to a PVDF membrane, dried, and blocked with 1% non-fat milk. The antibodies used were sheep anti-11b-HSD2 and anti-H6PDH polyclonal antibodies produced by us (Gomez-Sanchez et al 2001) and a rabbit anti11b-HSD1 polyclonal antibody kindly provided by Zigmund Krozowski (Brereton et al 2001). The blots were then incubated with peroxidase-labeled donkey anti-rabbit or anti-sheep second antibodies and developed using West Pico chemiluminescence substrate from Pierce Chemical Co. Liver and adipose tissue were the positive controls for 11b-HSD1 and H6PDH; kidney for 11b-HSD2.…”

Section: Western Blot Analysesmentioning

confidence: 99%

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Immunohistochemical Demonstration of the Mineralocorticoid Receptor, 11β-Hydroxysteroid Dehydrogenase-1 and −2, and Hexose-6-phosphate Dehydrogenase in Rat Ovary

Gómez-Sánchez

Gomez-Sanchez

Rodriguez

et al. 2009

J Histochem Cytochem.

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An IHC survey using several monoclonal antibodies against different portions of the rat mineralocorticoid receptor (MR) molecule demonstrated significant specific MR immunoreactivity in the ovary, prompting further study of the localization of MR and of determinants of extrinsic MR ligand specificity, 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2, and hexose-6-phosphate dehydrogenase (H6PDH). MR expression (real-time RT-PCR and Western blot) did not differ significantly in whole rat ovaries at early diestrus, late diestrus, estrus, and a few hours after ovulation. MR immunostaining was most intense in corporal lutea cells, light to moderate in oocytes and granulosa cells, and least intense in theca cells. Light immunoreactivity for 11β-HSD2 occurred in most cells, with some mural granulosa cells of mature follicles staining more strongly. The distribution of immunoreactivity for 11β-HSD1 and H6PDH required to generate NADPH, the cofactor required for reductase activity of 11β-HSD1, was similar, with the most-intense staining in the cytoplasm of corporal lutea and theca cells and light or no staining in the granulosa and oocytes. MR function in the ovary is as yet unclear, but distinct patterns of distribution of 11β-HSD1 and −2 and H6PDH suggest that the ligand for MR activation in different cells of the ovary may be differentially regulated. (J Histochem Cytochem 57:633–641, 2009)

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The 11β hydroxysteroid dehydrogenase 2 exists as an inactive dimer

Cited by 41 publications

References 24 publications

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

Impaired Protein Stability of 11β-Hydroxysteroid Dehydrogenase Type 2

Immunohistochemical Demonstration of the Mineralocorticoid Receptor, 11β-Hydroxysteroid Dehydrogenase-1 and −2, and Hexose-6-phosphate Dehydrogenase in Rat Ovary

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