Genomes and Genes
M C Holmes
Affiliation: University of Edinburgh
- 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...
- The role of 11beta-hydroxysteroid dehydrogenases in the brainMegan C Holmes
Endocrine Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Mol Cell Endocrinol 248:9-14. 2006..Loss of 11beta-HSD2 from the fetus and fetally derived tissues results in altered development of the cerebellum in the neonatal period and a life-long phenotype of anxiety, consistent with early life glucocorticoid programming...
- 11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoidsM C Holmes
Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Neuroscience 137:865-73. 2006..We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure...
- 11 Beta-hydroxysteroid dehydrogenases in the brain: two enzymes two rolesMegan C Holmes
Molecular Endocrinology, Molecular Medicine Centre, College of Medicine and Veterinary Sciences, University of Edinburgh, Edinburgh, United Kingdom
Ann N Y Acad Sci 1007:357-66. 2003..This review highlights the important and very different roles the two enzymes play in the brain, outlining recent results obtained from studying mice with a targeted gene deletion in the 11beta-HSD1 or 11beta-HSD2 genes...
- 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...
- 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...
- 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...
- Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiologyD O'Regan
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....
- 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...
- Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null miceN M Morton
Molecular Endocrinology, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Rd S, Edinburgh EH4 2XU, United Kingdom
J Biol Chem 276:41293-300. 2001..Further, 11beta-HSD-1(-/-) mice have improved glucose tolerance. These data suggest that 11beta-HSD-1 deficiency produces an improved lipid profile, hepatic insulin sensitization, and a potentially atheroprotective phenotype...
- 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...
- 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...
- 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 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...
- Altered placental methyl donor transport in the dexamethasone programmed ratC S Wyrwoll
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Placenta 33:220-3. 2012..These data suggest prenatal glucocorticoid overexposure causes complex alterations in the placental transport of key methyl donors which may have important implications for maternal diet and nutrient supplementation in pregnancy...
- 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...
- 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...
- Timed feeding of mice modulates light-entrained circadian rhythms of reticulated platelet abundance and plasma thrombopoietin and affects gene expression in megakaryocytesPaul S Hartley
Centre for Cardiovascular Science, Queen s Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Br J Haematol 146:185-92. 2009..These findings imply that circadian clock gene expression regulates platelet turnover in mammals...
- 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....
- 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...
- Overexpression of 5-HT2C receptors in forebrain leads to elevated anxiety and hypoactivityAtsuko Kimura
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen s Medical Research Institute, Edinburgh, Scotland
Eur J Neurosci 30:299-306. 2009..Our findings support a role for 5-HT(2C) receptor signalling in anxiety disorders. The C2CR mouse model offers a novel and effective approach for studying disorders associated with 5-HT(2C) receptors...
- Food-entrained rhythmic expression of PER2 and BMAL1 in murine megakaryocytes does not correlate with circadian rhythms in megakaryopoiesisP S Hartley
Centre for Cardiovascular Science, Queens Medical Research Institute, The University of Edinburgh, Edinburgh, UK
J Thromb Haemost 6:1144-52. 2008..Circadian rhythms control a vast array of biological processes in a broad spectrum of organisms. The contribution of circadian rhythms to the development of megakaryocytes and the regulation of platelet biology has not been defined...
- Glucocorticoid programming of pituitary-adrenal function: mechanisms and physiological consequencesL L Welberg
Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK
Semin Neonatol 6:319-29. 2001..Similar HPA axis hyperreactivity occurs in lower birth weight humans and may be an early manifestation of the 'low birth weight' phenotype...
- 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stressY Kotelevtsev
Centre for Genome Research, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh EH 9 3JQ, Scotland, UK
Proc Natl Acad Sci U S A 94:14924-9. 1997..The 11beta-HSD-1 -/- mice were found to resist hyperglycamia provoked by obesity or stress. Attenuation of hepatic 11beta-HSD-1 may provide a novel approach to the regulation of gluconeogenesis...
- 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...
- Mineralocorticoid and glucocorticoid receptor balance in control of HPA axis and behaviourA P Harris
Endocrinology Unit, Centre for Cardiovascular Science, The Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK Electronic address
Psychoneuroendocrinology 38:648-58. 2013..Since modulation of HPA-axis and behavioural dysfunction associated with high levels of MR, selective ligands or transcriptional regulators may afford novel therapeutic approaches to affective psychopathologies...
- Glioma tumourgenicity is decreased by iNOS knockout: experimental studies using the C6 striatal implantation glioma modelS Yamaguchi
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
Br J Neurosurg 16:567-72. 2002..The mechanisms that cause failure of tumour growth need clarification prior to considering that specific iNOS inhibitors might be candidates for adjuvant treatment of malignant glioma...
- 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...
- Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndromeUlrike A Nuber
Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany
Hum Mol Genet 14:2247-56. 2005..Given the known deleterious effect of glucocorticoid exposure on brain development, our data raise the possibility that disruption of MeCP2-dependent regulation of stress-responsive genes contributes to the symptoms of RTT...
- Divergent physical activity and novel alternative responses to high fat feeding in polygenic fat and lean miceMatjaz Simoncic
Biotechnical Faculty, Zootechnical Department, University of Ljubljana, 1230, Domzale, Slovenia
Behav Genet 38:292-300. 2008....
- Expression of interleukin-6 messenger RNA in a rat model of diffuse axonal injuryJonathan K J Rhodes
Department of Molecular Endocrinology, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK
Neurosci Lett 335:1-4. 2002..Cells strongly expressing IL-6 mRNA were also seen in the dentate gyrus. This inflammatory cytokine is clearly implicated in the response to CNS injury, but whether this response is neuroprotective or pathological is uncertain...
- Disruption of Ledgf/Psip1 results in perinatal mortality and homeotic skeletal transformationsHeidi G Sutherland
MRC Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, United Kingdom
Mol Cell Biol 26:7201-10. 2006..The latter phenotypes suggest a role for Psip1 in the control of Hox expression and may also explain why PSIP1 (LEDGF) is found as a fusion partner with NUP98 in myeloid leukemias...