Research Topics
Genomes and Genes
| Jonathan R SecklSummaryAffiliation: University of Edinburgh Country: UK Publications
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Publications
Glucocorticoid programmingJonathan R Seckl
Endocrinology Unit, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, EH4 2XU, UK
Ann N Y Acad Sci 1032:63-84. 2004..Overall, the data suggest that either pharmacological or physiological exposure to excess glucocorticoids prenatally programs pathologies in adult life...
11 beta-hydroxysteroid dehydrogenase type 1 induction in the arcuate nucleus by high-fat feeding: A novel constraint to hyperphagia?Valerie S Densmore
Endocrinology Unit, Queen s Medical Research Institute, Edinburgh EH16 4TJ, Scotland, United Kingdom
Endocrinology 147:4486-95. 2006..These data suggest that 11 beta-HSD1 in brain plays a role in the adaptive restraint of excess fat intake, in part by increasing inhibitory opioid tone on AGRP expression in the arcuate nucleus...
Glucocorticoids, developmental 'programming' and the risk of affective dysfunctionJonathan R Seckl
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, Edinburgh, UK
Prog Brain Res 167:17-34. 2008..Posttraumatic stress disorder and other affective diseases may both act as environmental challenges if present in early life and may themselves be more likely in individuals made 'vulnerable' by early life stress...
Cerebrospinal fluid cortisol levels are higher in patients with delirium versus controlsAndrew Pearson
Geriatric Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK
BMC Res Notes 3:33. 2010..abstract:..
Association between umbilical cord glucocorticoids and blood pressure at age 3 yearsSusanna Y Huh
Division of Gastroenterology and Nutrition, Children s Hospital Boston, Boston, MA, USA
BMC Med 6:25. 2008..Data in humans are limited. We examined in humans the association between venous umbilical cord blood glucocorticoids, a potential marker for placental 11beta-HSD2 enzyme activity, and blood pressure at age 3 years...
Medical and physiological aspects of the 11beta-hydroxysteroid dehydrogenase systemJ R Seckl
Molecular Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, UK
Eur J Biochem 249:361-4. 1997..Both isozymes are regulated during ontogeny and by a series of hormonal and other factors. 11Beta-HSD provide an important control of glucocorticoid action at a cellular level, and may represent new targets for therapeutic intervention...
Glucocorticoid "programming" and PTSD riskJonathan R Seckl
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Ann N Y Acad Sci 1071:351-78. 2006....
Prenatal glucocorticoids and long-term programmingJonathan R Seckl
Endocrinology Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
Eur J Endocrinol 151:U49-62. 2004..Overall, the data suggest that both pharmacological and physiological exposure prenatally to excess glucocorticoids programmes cardiovascular, metabolic and neuroendocrine disorders in adult life...
Physiologic programming of the fetusJ R Seckl
Molecular Medicine Centre, University of Edinburgh, Western General Hospital, United Kingdom, USA
Clin Perinatol 25:939-62, vii. 1998....
Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid actionJ R Seckl
Endocrinology Unit, Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom
Endocrinology 142:1371-6. 2001..Inhibition of 11beta-HSD1 represents a potential target for therapy of disorders that might be ameliorated by local reduction of glucocorticoid action, including type 2 diabetes, obesity, and age-related cognitive dysfunction...
Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programmingJ R Seckl
Molecular Medicine Center, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, United Kingdom
Kidney Int 57:1412-7. 2000..Thus, glucocorticoid programming may explain, in part, the association between fetal events and subsequent disorders in adult life...
11beta-hydroxysteroid dehydrogenase type 1 as a modulator of glucocorticoid action: from metabolism to memoryJonathan R Seckl
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK
Trends Endocrinol Metab 15:418-24. 2004..The ongoing development of selective 11beta-HSD1 inhibitors affords the opportunity to explore a new approach to some major common disorders...
11beta-hydroxysteroid dehydrogenases: changing glucocorticoid actionJonathan R Seckl
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK
Curr Opin Pharmacol 4:597-602. 2004..Overexpression of this isozyme may contribute to the pathogenesis of the metabolic syndrome. Its inhibition is a potential therapeutic target for both metabolic and glucocorticoid-associated CNS disorders...
Minireview: Stress-related psychiatric disorders with low cortisol levels: a metabolic hypothesisRachel Yehuda
Mount Sinai School of Medicine, Department of Psychiatry, Traumatology and Stress Studies Division, New York, New York 10029, USA
Endocrinology 152:4496-503. 2011..This notion implies a vulnerable early-life phenotype may be discernable and indicates potential therapy by modest glucocorticoid replacement. Indeed, early clinical trials with cortisol have shown a modicum of promise...
11Beta-hydroxysteroid dehydrogenases: a novel control of glucocorticoid action in the brainJonathan R Seckl
Endocrinology Unit, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, UK
Endocr Res 28:701-7. 2002..The striking protection against cognitive decline seen in elderly 11beta-HSD1 knockout mice suggest that manipulation of this isozyme may be a useful therapeutic avenue to explore...
11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?J R Seckl
Department of Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom
Front Neuroendocrinol 18:49-99. 1997..Enzyme modulation by pharmacological or other agents may provide a useful means to target increased or attenuated glucocorticoid action to specific sites in the brain...
Glucocorticoid programming of the fetus; adult phenotypes and molecular mechanismsJ R Seckl
Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
Mol Cell Endocrinol 185:61-71. 2001..Detailed molecular mechanisms are being dissected. Analogous stress axis hyperreactivity occurs in lower birth weight humans and may be an early manifestation and indicate approaches to manipulation or prevention of the phenotype...
Prenatal dexamethasone programs expression of genes in liver and adipose tissue and increased hepatic lipid accumulation but not obesity on a high-fat dietAmanda J Drake
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
Endocrinology 151:1581-7. 2010..This may be due to depot-specific-programmed alterations in fat metabolism in adipose tissue...
Dietary manipulation reveals an unexpected inverse relationship between fat mass and adipose 11β-hydroxysteroid dehydrogenase type 1Tak Yung Man
Endocrinology Unit, Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Am J Physiol Endocrinol Metab 300:E1076-84. 2011..The dynamic depot-selective relationship between adipose 11β-HSD1 and fat mass strongly implicates a dominant physiological role for local tissue glucocorticoid reactivation in fat mobilization...
Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient miceNicholas M Morton
Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK
Diabetes 53:931-8. 2004..These data provide the first in vivo evidence that adipose 11 beta-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11 beta-HSD-1 deficiency or inhibition...
11beta-hydroxysteroid dehydrogenase type 1 expression is increased in the aged mouse hippocampus and parietal cortex and causes memory impairmentsMegan C Holmes
Endocrinology Unit, University of Edinburgh, Queen s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom
J Neurosci 30:6916-20. 2010..Thus, excess 11beta-HSD1 in forebrain is a cause of as well as a therapeutic target in memory impairments with aging...
11beta-hydroxysteroid dehydrogenase type 1 and obesityNicholas M Morton
Endocrinology Unit, Centre for Cardiovascular Sciences, Queens Medical Research Institute, Edinburgh University, Edinburgh, UK
Front Horm Res 36:146-64. 2008....
A polygenic model of the metabolic syndrome with reduced circulating and intra-adipose glucocorticoid actionNicholas M Morton
Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, UK
Diabetes 54:3371-8. 2005..Our data suggest that idiopathic metabolic syndrome might associate with such a novel pattern of glucocorticoid action and sensitivity in humans, with implications for tissue-specific therapeutic targeting of 11beta-HSD-1...
Partial deficiency or short-term inhibition of 11beta-hydroxysteroid dehydrogenase type 1 improves cognitive function in aging miceKaren Sooy
Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, Edinburgh, United Kingdom
J Neurosci 30:13867-72. 2010..These data support the use of selective 11β-HSD1 inhibitors in the treatment of age-related cognitive impairments...
Reduced adipose glucocorticoid reactivation and increased hepatic glucocorticoid clearance as an early adaptation to high-fat feeding in Wistar ratsAmanda J Drake
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
Endocrinology 146:913-9. 2005..Acute exposure to HF diet alters glucocorticoid metabolism, predicting lower hepatic and adipose intracellular glucocorticoid concentrations, which may be a key mechanism protecting against the metabolic complications of obesity...
Liver-selective transgene rescue of hypothalamic-pituitary-adrenal axis dysfunction in 11beta-hydroxysteroid dehydrogenase type 1-deficient miceJanice M Paterson
Centre for Cardiovascular Science, Endocrinology Unit, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom
Endocrinology 148:961-6. 2007..Therefore, hepatic glucocorticoid metabolism influences basal as well as stress-associated functions of the HPA axis...
Prenatal programming of metabolic syndrome in the common marmoset is associated with increased expression of 11beta-hydroxysteroid dehydrogenase type 1Moffat J Nyirenda
Endocrinology Unit, Queen s Medical Research Institute, University of Edinburgh, U K
Diabetes 58:2873-9. 2009..Here, we tested whether 11beta-HSD1 expression, like the metabolic syndrome, is "programmed" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey...
Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosteroneZoi Michailidou
Endocrine Unit, Queen s Medical Research Institute, Centre for Cardiovascular Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
J Endocrinol 194:161-70. 2007..These data suggest that CORT-inducible 11beta-HSD1 expression in fat contributes to the adverse cardiometabolic effects of CORT in POMC deficiency, whereas higher GR levels may be more important in liver...
Leptin levels and depressive symptoms in people with type 2 diabetes: the edinburgh type 2 diabetes studyJavier Labad
Endocrinology Unit, Centre for Cardiovascular Sciences, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK
Psychosom Med 74:39-45. 2012..We sought to assess whether leptin is related to depressive symptoms in people with Type 2 diabetes...
Enhanced hippocampal long-term potentiation and spatial learning in aged 11beta-hydroxysteroid dehydrogenase type 1 knock-out miceJoyce L W Yau
Endocrinology Unit, Molecular University of Edinburgh, Queen s Medical Research Institute, EH16 4TJ Edinburgh, United Kingdom
J Neurosci 27:10487-96. 2007..These data suggest that 11beta-HSD1 deficiency enhances synaptic potentiation in the aged hippocampus and this may underlie the better maintenance of learning and memory with aging, which occurs in the absence of increased neurogenesis...
Forebrain mineralocorticoid receptor overexpression enhances memory, reduces anxiety and attenuates neuronal loss in cerebral ischaemiaMaggie Lai
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, Edinburgh, UK
Eur J Neurosci 25:1832-42. 2007..The induction of neuronal MR appears to offer a protective response which has potential therapeutic implications in cerebral ischaemia and cognitive and affective disorders...
Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesityErin E Kershaw
Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 54:1023-31. 2005..These data suggest that reduction of active GCs exclusively in adipose tissue is an important determinant of a favorable metabolic phenotype with respect to energy homeostasis and the metabolic syndrome...
Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitizationMark Nixon
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, Edinburgh, Scotland, U K
Diabetes 61:790-6. 2012..Reduced intra-adipose glucocorticoid regeneration by 11β-HSD1 is a novel mechanism that contributes to the metabolic efficacy of salicylates...
11β-hydroxysteroid dehydrogenase type 1, brain atrophy and cognitive declineAlasdair M J MacLullich
Endocrinology, University of Edinburgh, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh, Scotland, UK
Neurobiol Aging 33:207.e1-8. 2012..55, p = 0.0002) over 6 years. The predictive link between systemic 11β-HSD1 activity and progressive brain atrophy and cognitive decline suggests 11β-HSD1 inhibition as a plausible therapy for brain aging...
Morning cortisol levels and cognitive abilities in people with type 2 diabetes: the Edinburgh type 2 diabetes studyRebecca M Reynolds
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Diabetes Care 33:714-20. 2010..We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes...
11beta-hydroxysteroid dehydrogenase type 1 deficiency prevents memory deficits with aging by switching from glucocorticoid receptor to mineralocorticoid receptor-mediated cognitive controlJoyce L W Yau
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, and Endocrinology Unit, Centre for Cardiovascular Science, The Queen s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom
J Neurosci 31:4188-93. 2011....
11beta-hydroxysteroid dehydrogenase type 1 as a novel therapeutic target in metabolic and neurodegenerative diseaseBrian R Walker
University of Edinburgh, Endocrinology Unit, Western General Hospital, Edinburgh EH4 2XU, UK
Expert Opin Ther Targets 7:771-83. 2003..The clinical development of potent selective 11HSD1 inhibitors is now a high priority...
7-oxysterols modulate glucocorticoid activity in adipocytes through competition for 11beta-hydroxysteroid dehydrogenase typeMalgorzata Wamil
Endocrinology Unit, Centre for Cardiovascular Science, The Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
Endocrinology 149:5909-18. 2008..Thus, the activity and reaction direction of adipose 11beta-HSD1 is altered under conditions of oxysterol excess, and could impact upon the pathophysiology of obesity and its complications...
Plasma cortisol levels, brain volumes and cognition in healthy elderly menAlasdair M J MacLullich
Geriatric Medicine, University of Edinburgh, Room SU220, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
Psychoneuroendocrinology 30:505-15. 2005..CONCLUSIONS: In healthy older men, higher plasma cortisol levels are associated with worse ageing-related overall cognitive change but not ageing-related brain atrophy...
Prenatal dexamethasone 'programmes' hypotension, but stress-induced hypertension in adult offspringDavid O'Regan
Endocrinology Unit, Queen s Medical Research Institute, Centre for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
J Endocrinol 196:343-52. 2008..We therefore conclude that altered sympathetic responses mediate the stress-induced hypertension associated with prenatal DEX programming...
11beta-hydroxysteroid dehydrogenase type 2 in mouse aorta: localization and influence on response to glucocorticoidsClare Christy
School of Molecular and Clinical Medicine, Endocrinology Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK
Hypertension 42:580-7. 2003..Therefore, additional mechanisms, possibly involving indirect effects of enhanced corticosterone action in the kidney and the resultant hypertension, must be involved...
Obese Zucker rats have reduced mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 1 expression in hippocampus-implications for dysregulation of the hypothalamic-pituitary-adrenal axis in obesityCecilia Mattsson
Endocrinology Unit, Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom
Endocrinology 144:2997-3003. 2003..This may be exacerbated by impaired local regeneration of corticosterone by 11betaHSD1. These abnormalities could contribute to the subtle changes in the HPA axis in rodent and human obesity...
The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice provide evidence for direct fetal programming of behavior by endogenous glucocorticoidsMegan C Holmes
Endocrinology Unit, Centre for Cardiovascular Disease, Queen s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
J Neurosci 26:3840-4. 2006..This provides clear evidence for the key role of fetoplacental 11beta-HSD2 in prenatal glucocorticoid programming...
A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genesNicholas M Morton
Molecular Metabolism Group, BHF University Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, Edinburgh, United Kingdom
PLoS ONE 6:e23944. 2011....
Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic miceJanice M Paterson
Wellcome Trust CVRI Molecular Physiology Group, University of Edinburgh Medical School, Wilkie Building, Teviot Place, Edinburgh EH8 9AG, Scotland, United Kingdom
Proc Natl Acad Sci U S A 101:7088-93. 2004....
Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout miceCaitlin S Wyrwoll
Endocrinology Unit, Queen s Medical Research Institute, Centre for Cardiovascular Science, Edinburgh, United Kingdom
Endocrinology 150:1287-93. 2009..Our data suggest that restriction of fetal growth in 11beta-HSD2(-/-) mice is mediated, at least in part, via altered placental transport of nutrients and reduction in placental vascularization...
Developmental and tissue-specific regulation of hepatocyte nuclear factor 4-alpha (HNF4-alpha) isoforms in rodentsSamena Dean
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Gene Expr 14:337-44. 2010....
Programming of rat muscle and fat metabolism by in utero overexposure to glucocorticoidsMark E Cleasby
Endocrinology Unit, Department of Medical Sciences, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, United Kingdom
Endocrinology 144:999-1007. 2003..However, increased GR and attenuated fatty acid uptake specifically in visceral adipose are consistent with insulin resistance in this crucial metabolic depot and could indirectly contribute to increased hepatic glucose output...
Tissue-specific messenger ribonucleic acid expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 and the glucocorticoid receptor within rat placenta suggests exquisite local control of glucocorticoid actionB J Waddell
Department of Medicine, The University of Edinburgh, Western General Hospital, Scotland, United Kingdom
Endocrinology 139:1517-23. 1998..Moreover, the changes in 11beta-HSD expression appear to be unrelated to development of the fetal adrenal cortex and are likely to reduce the placental glucocorticoid barrier near the end of pregnancy...
Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissueJonathan R Seckl
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom
Recent Prog Horm Res 59:359-93. 2004..Adipose 11beta-HSD1 deficiency contributes to a protective metabolic phenotype, supporting its role as a therapeutic target for the metabolic syndrome...
11β-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in miceAgnes E Coutinho
Centre for Cardiovascular Sciences, Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
Endocrinology 153:234-40. 2012..In contrast, 11β-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11β-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy...
Increased Angiogenesis Protects against Adipose Hypoxia and Fibrosis in Metabolic Disease-resistant 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD1)-deficient MiceZoi Michailidou
From the Medical Research Council MRC Centre for Inflammation Research and
J Biol Chem 287:4188-97. 2012..Improved adipose angiogenesis and reduced fibrosis provide a novel mechanism whereby suppression of intracellular glucocorticoid regeneration promotes safer fat expansion with weight gain...
Optimal elevation of β-cell 11β-hydroxysteroid dehydrogenase type 1 is a compensatory mechanism that prevents high-fat diet-induced β-cell failureSophie Turban
Molecular Metabolism Group, University of Edinburgh British Heart Foundation Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Diabetes 61:642-52. 2012..These findings have immediate significance for current therapeutic strategies for type 2 diabetes...
Reconciling the nutritional and glucocorticoid hypotheses of fetal programmingElizabeth C Cottrell
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
FASEB J 26:1866-74. 2012..Thus, maternal malnutrition and placental 11β-HSD2 deficiency act via distinct processes to retard fetal growth, both involving fetoplacental overexposure to glucocorticoids but from distinct sources...
Smaller left anterior cingulate cortex volumes are associated with impaired hypothalamic-pituitary-adrenal axis regulation in healthy elderly menAlasdair M J MacLullich
Endocrinology Unit, Center for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom
J Clin Endocrinol Metab 91:1591-4. 2006..Studies in animals suggest that the limbic prefrontal cortex, including the anterior cingulate cortex, is involved in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, but human data are lacking...
The antidepressant desipramine requires the ABCB1 (Mdr1)-type p-glycoprotein to upregulate the glucocorticoid receptor in miceJoyce L W Yau
Endocrinology Unit, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Neuropsychopharmacology 32:2520-9. 2007..These data support the notion that the MDR PGP is one of the molecular targets through which antidepressants regulate the HPA axis...
Is programming of glucocorticoid receptor expression by prenatal dexamethasone in the rat secondary to metabolic derangement in adulthood?Mark E Cleasby
Endocrinology Unit, Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
Eur J Endocrinol 148:129-38. 2003..However, cause and effect between altered GR expression, hypercorticosteronaemia, and hyperinsulinaemia remains to be established...
Local amplification of glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytesJames S Gilmour
Endocrinology Unit, Centre for Cardiovascular Sciences, Centre for Cardiovascular Sciences, The Queen s Medical Research Institute, University of Edinburgh, UK
J Immunol 176:7605-11. 2006..These data point to an early role for 11beta-HSD1 in promoting the rapid clearance of apoptotic cells during the resolution of inflammation and indicate a novel target for therapy...
Prenatal overexposure to glucocorticoids programs renal 11β-hydroxysteroid dehydrogenase type 2 expression and salt-sensitive hypertension in the ratJustin I Tang
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK
J Hypertens 29:282-9. 2011..Prenatal glucocorticoid excess programs hypertension in adulthood. The underlying mechanisms are unknown. Here, we tested whether hypertension in this model is due to increased renal mineralocorticoid activity...
The role and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in the inflammatory responseKaren E Chapman
Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Mol Cell Endocrinol 301:123-31. 2009..Finally, the mechanisms that regulate 11beta-HSD1 transcription will be discussed...
Elevated fasting plasma cortisol is associated with ischemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes studyRebecca M Reynolds
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
J Clin Endocrinol Metab 95:1602-8. 2010..People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk...
Novel fat depot-specific mechanisms underlie resistance to visceral obesity and inflammation in 11 β-hydroxysteroid dehydrogenase type 1-deficient miceMalgorzata Wamil
Endocrinology Unit, University of Edinburgh, Queen s Medical Research Institute, Edinburgh, Scotland
Diabetes 60:1158-67. 2011....
Prenatal glucocorticoid overexposure causes permanent increases in renal erythropoietin expression and red blood cell mass in the rat offspringJustin I Tang
Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4 TJ, Scotland, United Kingdom
Endocrinology 152:2716-21. 2011..These data indicate that RBC mass can be programmed by prenatal glucocorticoid excess, and if extrapolatable to humans, provide a novel mechanism for fetal origins of polycythemia and its associated complications...
Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in ratsAmanda J Drake
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Molecular Medicine Center, Western General Hospital, United Kingdom
Am J Physiol Regul Integr Comp Physiol 288:R34-8. 2005....
A transgenic model of visceral obesity and the metabolic syndromeH Masuzaki
Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA
Science 294:2166-70. 2001..Increased adipocyte 11beta HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome...
Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiologyC J Kenyon
Endocrinology Unit, Molecular Medicine Centre, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK
Am J Physiol Endocrinol Metab 287:E863-70. 2004....
Size of the neocerebellar vermis is associated with cognition in healthy elderly menAlasdair M J MacLullich
Geriatric Medicine Unit, University of Edinburgh, Room SU220, The Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
Brain Cogn 56:344-8. 2004..Total cerebellar volumes correlated significantly with a test of nonverbal reasoning (r=.030, p=.42). These findings suggest a specific association of neocerebellar vermis size with variations in cognitive ability in older adults...
Glucocorticoid regulation of the promoter of 11beta-hydroxysteroid dehydrogenase type 1 is indirect and requires CCAAT/enhancer-binding protein-betaShuji Sai
Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
Mol Endocrinol 22:2049-60. 2008..Positive regulation of 11beta-HSD1 by C/EBPbeta may link amplification of glucocorticoid action with metabolic and inflammatory pathways and may represent an endogenous innate host-defense mechanism...
Polymorphisms in the gene encoding 11B-hydroxysteroid dehydrogenase type 1 (HSD11B1) and lifetime cognitive changeIan J Deary
Department of Psychology, University of Edinburgh, 7 George Square, UK
Neurosci Lett 393:74-7. 2006..91) and rs846910-A/G (p=.90) between the groups. We conclude that these variants in HSD11B1 are not significant contributors to the range of cognitive ageing examined here...
A switch in the mechanism of hypertension in the syndrome of apparent mineralocorticoid excessMatthew A Bailey
Centre for Cardiovascular Science, The University of Edinburgh, QMRI, 47, Little France Crescent, Edinburgh, EH16 4TJ, UK
J Am Soc Nephrol 19:47-58. 2008..In summary, it is proposed that renal sodium retention remains a key event in apparent mineralocorticoid excess but that the accompanying hypertension changes from a renal to a vascular etiology over time...
Omental 11beta-hydroxysteroid dehydrogenase 1 correlates with fat cell size independently of obesityZoi Michailidou
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Obesity (Silver Spring) 15:1155-63. 2007..Our objective was to determine the association between 11betaHSD1 and GRalpha mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome...
Injury-induced mineralocorticoid receptor expression involves differential promoter usage: a novel role for the rat MRbeta variantPeng Kang
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Scotland, UK
Mol Cell Endocrinol 305:56-62. 2009..These results demonstrate a novel key role for the MRbeta transcript in response to injury and suggest that some of the known neuroprotective effects of hypothermia may be mediated through increased MR expression...
Mineralocorticoid receptor expression and increased survival following neuronal injuryMalcolm R Macleod
Endocrinology Unit, Molecular Medicine Centre, Edinburgh University, Scotland
Eur J Neurosci 17:1549-55. 2003..Modulation of mineralocorticoid receptor gene expression may therefore be an important target for reduction of brain injury in conditions caused by cerebral ischaemia including brain damage following cardiac arrest and stroke...
Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null miceW John Sheward
Centre for Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom
J Neurosci 27:4351-8. 2007..Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock...
11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabeticsThekkepat C Sandeep
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
Proc Natl Acad Sci U S A 101:6734-9. 2004..11beta-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline...
11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle and heart: implications for cardiovascular responses to glucocorticoidsB R Walker
University of Edinburgh, Department of Medicine, Western General Hospital, United Kingdom
Endocrinology 129:3305-12. 1991..Thus, 11 beta-OHSD is appropriately sited to modulate access of corticosterone to vascular receptors and could influence vascular resistance, cardiac output and thereby blood pressure...
Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during developmentH J L Speirs
Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, UK
J Endocrinol 181:105-16. 2004....
Prenatal glucocorticoid programming of brain corticosteroid receptors and corticotrophin-releasing hormone: possible implications for behaviourL A Welberg
Molecular Endocrinology Laboratory, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, EH4 2XU, Scotland, Edinburgh, UK
Neuroscience 104:71-9. 2001..Overexposure to glucocorticoids, especially late in gestation, may explain the link between reduced early growth and adult affective dysfunction...
11β-hydroxysteroid dehydrogenase type 2 deficiency accelerates atherogenesis and causes proinflammatory changes in the endothelium in apoe-/- miceGraeme A Deuchar
Centre for Cardiovascular Science, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
Endocrinology 152:236-46. 2011..Thus, loss of 11β-HSD2 leads to striking atherogenesis associated with activation of MR, stimulating proinflammatory processes in the endothelium of E/b2 mice...
Assessing the HPA axis in patients with pituitary disease: a UK surveyRebecca M Reynolds
Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, Queen s Medical Research Institute, Little France Crescent, Edinburgh EH16 4TJ, UK
Clin Endocrinol (Oxf) 64:82-5. 2006....
The role of corticosterone in human hypothalamic-pituitary-adrenal axis feedbackPeter J Raubenheimer
Department of Endocrinology, University of Edinburgh, Centre for Cardiovascular Science, The Queen s Medical Research Institute, Edinburgh, UK
Clin Endocrinol (Oxf) 65:22-6. 2006..Additionally, the relative affinities for the glucocorticoid and mineralocorticoid receptors differ, such that corticosterone may play a significant role in human brain function...
Altered peripheral sensitivity to glucocorticoids in primary open-angle glaucomaJohn Stokes
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, U K
Invest Ophthalmol Vis Sci 44:5163-7. 2003..This study was an investigation of the central and peripheral sensitivity to glucocorticoids in patients with POAG or ocular hypertension (OHT) and the differential metabolism of glucocorticoids by 11beta-HSDs...
Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 as a promising therapeutic targetMalgorzata Wamil
Endocrinology Unit, Centre for Cardiovascular Science, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Drug Discov Today 12:504-20. 2007..11beta-HSD1 null mice also resist cognitive decline with ageing, and this is seen in humans with a prototypic inhibitor. Thus 11beta-HSD1 inhibition is an emerging pleiotropic therapeutic target...
Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat dietZ Michailidou
Endocrinology Unit, Centre for Cardiovascular Sciences, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
FASEB J 22:3896-907. 2008..Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet...
5'-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: differential regulation of variant transcripts by early-life eventsJ A McCormick
Molecular Endocrinology, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, United Kingdom
Mol Endocrinol 14:506-17. 2000..Such tissue specificity of promoter usage allows differential GR regulation and programming...
Intracellular regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-1 plays a key role in regulation of the hypothalamic-pituitary-adrenal axis: analysis of 11beta-HSD-1-deficient miceH J Harris
Molecular Endocrinology, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, Scotland, United Kingdom
Endocrinology 142:114-20. 2001..Thus 11beta-HSD-1 amplifies glucocorticoid feedback on the HPA axis and is an important regulator of neuronal glucocorticoid exposure under both basal and stress conditions in vivo...
Phenotypic analysis of mice bearing targeted deletions of 11beta-hydroxysteroid dehydrogenases 1 and 2 genesM C Holmes
Molecular Endocrinology, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Mol Cell Endocrinol 171:15-20. 2001..Overall, these transgenic models have proved very useful for elucidating the roles of 11beta-HSDs in vivo and will be a unique resource for investigating the importance of each enzyme in the diverse actions of glucocorticoids...
Cloning, sequencing and tissue-distribution of mouse 11 beta-hydroxysteroid dehydrogenase-1 cDNAV Rajan
Department of Medicine, University of Edinburgh, Western General Hospital, U K
J Steroid Biochem Mol Biol 52:141-7. 1995..Thus, despite the high inter-species conservation of 11 beta-HSD1, there are clear species and tissue-specific differences in its expression...
Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylationK Rose
Centre for Genome Research and Centre for Neuroscience, University of Edinburgh, King s Buildings, Edinburgh EH9 3JQ, United Kingdom
J Biol Chem 276:23937-44. 2001..CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and provides the predominant route for local metabolism of DHEA and related molecules in brain and other tissues...
C/EBP regulates hepatic transcription of 11beta -hydroxysteroid dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathwaysL J Williams
Molecular Endocrinology Group, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom
J Biol Chem 275:30232-9. 2000....
Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2R W Brown
University Department of Medicine, Western General Hospital, Edinburgh, Scotland, UK
Biochem J 313:1007-17. 1996..11 beta-HSD2 transcripts are expressed in fetal kidney (but not lung, liver or brain) at 21-26 weeks, suggesting that an 11 beta-HSD2 distribution resembling that in the adult is established by this stage in human development...
Modulation of oestrogen receptor-beta mRNA expression in rat paraventricular and supraoptic nucleus neurones following adrenal steroid manipulation and hyperosmotic stimulationS J Somponpun
Laboratory of Neuroendocrinology, Division of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK
J Neuroendocrinol 16:472-82. 2004..Consequently, regulation of oxytocin and vasopressin neurone activity via ERbeta is expected to vary according to their functional state and, in particular, on basal glucocorticoid actions...
Programming the offspring of the pig by prenatal social stress: neuroendocrine activity and behaviourSusan Jarvis
Animal Behaviour and Welfare, Sustainable Livestock Systems, Scottish Agricultural College, Edinburgh, UK
Horm Behav 49:68-80. 2006..Indeed, Mix 2 and Mix 3 daughters also tended to bite at their piglets more than control daughters...
Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in miceHiroaki Masuzaki
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 112:83-90. 2003..The potential role of adipose 11beta-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder...
Hypothalamic-pituitary-adrenal axis abnormalities in response to deletion of 11beta-HSD1 is strain-dependentR N Carter
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
J Neuroendocrinol 21:879-87. 2009..Similar variations in plasticity may underpin inter-individual differences in vulnerability to disorders associated with HPA axis dysregulation. They also indicate that 11beta-HSD1 inhibition does not inevitably activate the HPA axis...
Differential promoter usage by the rat 11 beta-hydroxysteroid dehydrogenase geneM P Moisan
University of Edinburgh, Department of Medicine, Western General Hospital, Scotland
Mol Endocrinol 6:1082-7. 1992....
CYP7B generates a selective estrogen receptor beta agonist in human prostateCecile Martin
Endocrinology Unit, Department of Oncology, University of Edinburgh Western General Hospital, Edinburgh EH4 2XU, United Kingdom
J Clin Endocrinol Metab 89:2928-35. 2004..By this reaction, an ERbeta-specific agonist, 7HD, is produced. Therefore, CYP7B may be a novel regulator of the androgens/estrogenic balance within the prostate...
Down-regulation of adipose 11beta-hydroxysteroid dehydrogenase type 1 by high-fat feeding in mice: a potential adaptive mechanism counteracting metabolic diseaseNicholas M Morton
Endocrinology Unit, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, Scotland, United Kingdom
Endocrinology 145:2707-12. 2004..Adaptive down-regulation of adipose 11beta-HSD-1 in response to chronic HF represents a novel mechanism that may counteract metabolic disease...
Mechanisms of disease: glucocorticoids, their placental metabolism and fetal 'programming' of adult pathophysiologyJonathan R Seckl
College of Medicine and Veterinary Medicine, University of Edinburgh, UK
Nat Clin Pract Endocrinol Metab 3:479-88. 2007..Intriguingly, some of these effects seem to be inherited by subsequent generations that are unexposed to exogenous glucocorticoids at any point in their lifespan from fertilization, which implies that these epigenetic effects persist...
Glucocorticoids amplify dibutyl phthalate-induced disruption of testosterone production and male reproductive developmentAmanda J Drake
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
Endocrinology 150:5055-64. 2009..These findings suggest that exposure to common environmental chemicals in combination with, for example, maternal stress, may increase the risk of common male reproductive abnormalities, with implications for human populations...
Diabetes and cognitive decline: are steroids the missing link?Alasdair M J MacLullich
Endocrinology Unit, Centre for Cardiovascular Science, The Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Cell Metab 7:286-7. 2008..2008) shows that reducing glucocorticoid levels in rodent diabetes models prevents cognitive deficits and enhances neurogenesis and synaptic plasticity. The clinical relevance of these intriguing findings remains undetermined...
