Article
Biochemistry & Molecular Biology
Beom Jun Kim, Noo Ri Lee, Chung Hyeok Lee, Young Bin Lee, Sung Jay Choe, Solam Lee, Hyun Jee Hwang, Eunjung Kim, Gareth G. Lavery, Kyong-Oh Shin, Kyungho Park, Eung Ho Choi
Summary: Increased expression of 11 beta-HSD1 in aged skin leads to elevated levels of active glucocorticoids, suppressing sebaceous lipid biosynthesis and causing impaired epidermal permeability barrier.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Rahul Singh, Vijay Kumar Bhardwaj, Pralay Das, Rituraj Purohit
Summary: Aminoarylbenzosuberene (AAB) molecules were analyzed in silico to develop potent inhibitors for 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD1) protein. AAB4 molecule showed stronger interactions and binding affinity compared to the standard inhibitors.
CHEMICAL COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Connar S. J. Westgate, Keira Markey, James L. Mitchell, Andreas Yiangou, Rishi Singhal, Paul Stewart, Jeremy W. Tomlinson, Gareth G. Lavery, Susan P. Mollan, Alexandra J. Sinclair
Summary: This study investigates the basal glucocorticoid phenotype in idiopathic intracranial hypertension (IIH) and the effects of weight loss on the glucocorticoid phenotype. The study demonstrates elevated systemic and adipose 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1) activity in IIH patients, and weight loss following bariatric surgery reduces this activity and decreases intracranial pressure (ICP). These findings provide new insights into the phenotype of IIH and suggest metabolic dysregulation as a feature of the disease.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Review
Medicine, General & Internal
Jonathan Seckl
Summary: 11 beta-HSDs are enzymes that convert active 11-hydroxy glucocorticoids to their inert 11-keto forms. 11 beta-HSD2 inactivates glucocorticoids and has important roles in the kidney and developing foetal brain. In contrast, 11 beta-HSD1 amplifies active glucocorticoid levels in the brain and is associated with age-related cognitive decline.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Eva Kathrin Lamade, Ferdinand Hendlmeier, Stefan A. Wudy, Stephanie H. Witt, Marcella Rietschel, Michaela Coenen, Maria Gilles, Michael Deuschle
Summary: The study revealed time-specific alteration of fetoplacental 11 beta-HSD2 activity, peaking in the morning to protect fetus from maternal glucocorticoids. Acute affective or anxiety disorders were found to impact fetoplacental 11 beta-HSD2 activity.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Immunology
Rahul Y. Mahida, Sian Lax, Christopher R. Bassford, Aaron Scott, Dhruv Parekh, Rowan S. Hardy, Babu Naidu, Michael A. Matthay, Paul M. Stewart, Mark C. Cooper, Gavin D. Perkins, David R. Thickett
Summary: Acute Respiratory Distress Syndrome (ARDS) is a severe inflammatory lung disease commonly caused by sepsis. Glucocorticoids are immune-modulating steroids that can suppress inflammation. Impaired activity of 11 beta-hydroxysteroid dehydrogenase type-1 (HSD-1) and glucocorticoid activation in alveolar macrophages (AMs) may lead to greater inflammatory injury and worse outcomes in sepsis-related ARDS.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Hongguo Guan, Yiyan Wang, Huitao Li, Qiqi Zhu, Xiaoheng Li, Guang Liang, Ren-Shan Ge
Summary: WZS08 is a potent inhibitor of rat, mouse, and human 11 beta-hydroxysteroid dehydrogenase 1, effectively treating non-alcoholic fatty liver disease in mice by reducing liver fat content and improving liver morphology.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jiangang Cao, Yawen Chen, Hui Wang
Summary: Basal glucocorticoid levels play a crucial role in regulating fetal development and determining future outcomes. Adverse prenatal environments have been found to result in abnormal maternal glucocorticoid levels during pregnancy. 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), which are present in target organs of glucocorticoids and mineralocorticoids, are involved in fetal physiological and pathological development by activating or inactivating glucocorticoids. Several pathways can be affected by prenatal adverse environments, leading to abnormal local glucocorticoid levels, changes in fetal developmental programming and homeostasis, and increased susceptibility to various diseases after birth. This review provides a theoretical basis for the early prevention and treatment of fetal-originated diseases.
Article
Biochemistry & Molecular Biology
Martina Blaschke, Regine Koepp, Frank Streit, Johannes Beismann, Georg Manthey, Mark-Tilmann Seitz, Angelique Kragl, Heide Siggelkow
Summary: The enzyme 11 beta-HSD1 plays a key role in pre-receptor glucocorticoid metabolism, with increased expression leading to adipogenic differentiation in human mesenchymal progenitor cells. Inhibition experiments confirmed the enzyme's specificity for cortisol synthesis and adipogenic differentiation, potentially explaining the link between increased 11 beta-HSD1 expression, higher cortisol levels, and reduced bone quality in old age or in situations of supra-physiological glucocorticoid exposure.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Michael Weingartner, Simon Stucheli, Denise Kratschmar, Julia Birk, Petra Klusonova, Karen E. Chapman, Gareth G. Lavery, Alex Odermatt
Summary: The study found that the plasma ratio of UDC-Tau to 7oxoLC-Tau can serve as a biomarker for decreased 11 beta-HSD1 oxoreduction activity in different mouse models. Enzyme product to substrate ratios were more reliable markers of 11 beta-HSD1 activity than absolute levels due to large inter-individual variations in bile acid concentrations. The persistence of oxoreduction activity in the face of cofactor loss indicates the existence of an alternative NADPH source in the endoplasmic reticulum.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Cristina Gomez, Zerin Alimajstorovic, Nantia Othonos, Denise V. Winter, Sarah White, Gareth G. Lavery, Jeremy W. Tomlinson, Alexandra J. Sinclair, Alex Odermatt
Summary: This study compares the abilities of GUDCA/G7oxoLCA ratio and urinary (5α-THF+THF)/THE ratio to detect pharmacological 11 beta-HSD1 inhibition in humans. Results suggest that GUDCA/G7oxoLCA ratio is a more reliable biomarker for 11 beta-HSD1 inhibition.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zhixin Wu, Yinxian Wen, Hao Xiao, Jiayong Zhu, Bin Li, Yangfan Shangguan, Hangyuan He, Hui Wang, Liaobin Chen
Summary: Epidemiological investigations have shown an increased risk of osteoporosis in individuals treated with dexamethasone during pregnancy. Decreased peak bone mass and increased bone local active corticosterone were observed in prenatal dexamethasone exposure (PDE) offspring, with further decrease and increase after chronic stress. Injection of 118-HSD2 overexpression lentivirus partially alleviated bone loss induced by PDE. Dexamethasone inhibited 118HSD2 expression and aggravated the inhibitory effect of corticosterone on osteogenic differentiation, while overexpression of 118-HSD2 partially alleviated this effect.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Nutrition & Dietetics
Yuki Nouchi, Eiji Munetsuna, Hiroya Yamada, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Miyuki Ikeya, Itsuki Kageyama, Takuya Wakasugi, Atsushi Teshigawara, Yuji Hattori, Yoshiki Tsuboi, Hiroaki Ishikawa, Koji Suzuki, Koji Ohashi
Summary: This study aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring. By giving female Sprague Dawley rats HFCS solution, it was found that HFCS led to a decrease in activity of GC-metabolizing enzyme 11 beta-Hsd2 and an increase in renal miR-27a expression. These findings suggest that the elevation of circulating GC levels in offspring induced by maternal HFCS consumption may be explained by a decrease in 11 beta-Hsd2 activity via renal miR-27a expression.
Article
Biochemistry & Molecular Biology
Justine M. Webster, Michael S. Sagmeister, Chloe G. Fenton, Alex P. Seabright, Yu-Chiang Lai, Simon W. Jones, Andrew Filer, Mark S. Cooper, Gareth G. Lavery, Karim Raza, Ramon Langen, Rowan S. Hardy
Summary: Glucocorticoids are important anti-inflammatory therapies, but their use is limited due to metabolic adverse effects like muscle wasting. The enzyme 11 beta-HSD1 plays a role in modulating glucocorticoid responses in muscle. Knocking out 11 beta-HSD1 prevented muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation, suggesting a potential strategy to refine the safety of glucocorticoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Szymon Baumgart, Daria Kupczyk, Aneta Archala, Oliwia Koszla, Przemyslaw Solek, Wojciech Plazinski, Anita Plazinska, Renata Studzinska
Summary: In this study, a series of new 2-(cyclopentylamino)thiazol-4(5H)-one derivatives were synthesized and tested for their anticancer, antioxidant, and 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) inhibitory activities. The compounds showed significant anticancer activity against multiple cancer cell lines, as well as inhibitory effects on 11 beta-HSD1 isoform. Compound 3h exhibited the strongest inhibitory effect on 11 beta-HSD1 and was selected for further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)