scholarly journals Characterisation of the cancer-associated glucocorticoid system: key role of 11β-hydroxysteroid dehydrogenase type 2

2017 ◽  
Vol 117 (7) ◽  
pp. 984-993 ◽  
Author(s):  
Nicola Cirillo ◽  
David J Morgan ◽  
Maria Carmela Pedicillo ◽  
Antonio Celentano ◽  
Lorenzo Lo Muzio ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase

ROLE OF LOCAL 11beta-HYDROXYSTEROID DEHYDROGENASE TYPE 2 (HSD11B2) EXPRESSION IN DETERMINING THE PHENOTYPE OF ADRENAL ADENOMAS

2002 ◽  
Vol 28 (4) ◽  
pp. 751-752 ◽  
Author(s):  
Tomoatsu Mune ◽  
Hiroyuki Morita ◽  
Takashi Suzuki ◽  
Yoshihito Takahashi ◽  
Yukinori Isomura ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase

scholarly journals 11β-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action

2005 ◽  
Vol 186 (2) ◽  
pp. 251-271 ◽  
Author(s):  
Nicole Draper ◽  
Paul M Stewart
Keyword(s):  
Molecular Basis ◽  
Hydroxysteroid Dehydrogenase ◽  
Hormone Action ◽  
Enzyme Expression ◽  
Human Obesity ◽  
Corticosteroid Hormone

Two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2) catalyse the interconversion of hormonally active cortisol and inactive cortisone. The enzyme evolved from a metabolic pathway to a novel mechanism underpinning human disease with the elucidation of the role of the type 2 or ‘kidney’ isozyme and an inherited form of hypertension, ‘apparent mineralocorti-coid excess’. ‘Cushing’s disease of the kidney’ arises because of a failure of 11β-HSD2 to inactivate cortisol to cortisone resulting in cortisol-induced mineralocorticoid excess. Conversely, 11β-HSD1 has been linked to human obesity and insulin resistance, but also to other diseases in which glucocorticoids have historically been implicated (osteoporosis, glaucoma). Here, the activation of cortisol from cortisone facilitates glucocorticoid hormone action at an autocrine level. The molecular basis for the putative human 11β-HSD1 ‘knockout’ – ‘cortisone reductase deficiency’ - has recently been described, an observation that also answers a long standing conundrum relating to the set-point of 11β-HSD1 activity. In each case, these clinical studies have been underpinned by studies in vitro and the manipulation of enzyme expression in vivo using recombinant mouse models.

scholarly journals The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight1

2015 ◽  
Vol 92 (6) ◽  
Author(s):  
Benjamin B. Green ◽  
David A. Armstrong ◽  
Corina Lesseur ◽  
Alison G. Paquette ◽  
Dylan J. Guerin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hydroxysteroid Dehydrogenase ◽  
Infant Birth

scholarly journals The role of the heterocycle in bis(hydroxyphenyl)triazoles for inhibition of 17β-Hydroxysteroid Dehydrogenase (17β-HSD) type 1 and type 2

2009 ◽  
Vol 301 (1-2) ◽  
pp. 212-215 ◽  
Author(s):  
Yaseen A. Al-Soud ◽  
Emmanuel Bey ◽  
Alexander Oster ◽  
Sandrine Marchais-Oberwinkler ◽  
Ruth Werth ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase

scholarly journals A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta

2017 ◽  
Vol 292 (18) ◽  
pp. 7578-7587 ◽  
Author(s):  
Rujuan Zuo ◽  
Xiaohui Liu ◽  
Wangsheng Wang ◽  
Wenjiao Li ◽  
Hao Ying ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Histone H3 ◽  
Hydroxysteroid Dehydrogenase ◽  
Ezh2 Expression ◽  
Enhancer Of Zeste ◽  
E2f Transcription Factor ◽  
Pka Pathway ◽  
Transcription Factor 1

The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. Further studies revealed that, upon syncytialization, human chorionic gonadotropin reduced the phosphorylation of retinoblastoma protein (pRB) via activation of the cAMP/PKA pathway, which sequesters E2F transcription factor 1 (E2F1), the transcription factor for EZH2 expression. As a result of inactivation of the pRB-E2F1-EZH2 pathway, the repressive marker trimethylation of histone H3 lysine 27 at the 11β-HSD2 promoter is removed, which leads to the robust expression of 11β-HSD2 during syncytialization.

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