Tuckermann Laboratory

Tissue-specific hormone action

Tissue specific action of glucocorticoid hormone receptors and interacting factors in age related processes: stem cell renewal / differentiation, inflammation, osteoporosis

» Differential modes of glucocorticoid receptor (GR) action in the nucleus. The GR exerts in the nucleus two major types of gene regulation. 1) The GR binds as a dimer to response elements on the DNA of GC target genes and facilitates transcription by the recruitment of co-activators (p160/SRC, CBP and others, left). 2) The GR interacts with a monomer with pro-inflammatory acting transcription factors (AP-1, NF-kB, IRF-3), possibly by co-integrators such as TRIP6 or STAMP and thereby interferes with co-activator recruitment (CBP, GRIP-1 and others) important for pro-inflammatory gene expression.

Ageing of an organism is paralleled by the gradual failure and detoriation of several organs, such as the decay of muscle, bone and connective tissue, and changes in the immune system. Consequences include osteoporosis, enhanced adipogenesis, immune suppression and physiological alterations such as the metabolic syndrome. Intriguingly, pharmacologically applied glucocorticoids (GCs) exert similar catabolic effects on these organs. Thus, by understanding GC-mediated effects in organs and tissues, we may also learn about degenerative processes during ageing. Our aim is the deeper understanding of the action of GCs via their nuclear receptor (GR) in these age-related processes. We use a combinatorial approach employing functional characterization of mouse strains conditionally mutated both in the GR and selected target genes in disease models, together with the development of functional screening tools for relevant cell types in age-related disorders. Our goal is to decipher new mechanisms and to identify new mediators of therapeutic and side effects of GCs.

» Infiltrating macrophages (green) into inflamed skin in contact allergy are a target for GR activity for immune supression by GCs.

» Double calcein labelling of a vertebrae mouse bone in green fluorescence display the bone formation rate, which is inhibited by GCs via the GR in osteoblasts.

» Adipocytes labelled with Nile Red (stains lipid droplets in yellow) and DAPI (stains nuclei in blue) require the dimerized GR to promote adipogenesis.

Recent selected publications

Tuckermann J, Bourguet W, Mandrupp S (2010). Meeting Report: Nuclear Receptors: Transcription Factors and Drug Targets Connecting Basic Research with Translational Medicine. Mol Endocrinol, 24, 1311-21 [PubMed]
Rauch A, Seitz S, Baschant, U, Schilling AF, Illing A, Stride B, Kirilov M, Mandic V, Takacz A, Schmidt-Ullrich R, Ostermay S, Schinke T, Spanbroek R, Zaiss M, Angel PE, Lerner UH, David JP, Reichard HM, Amling M, Schütz G, Tuckermann J (2010). Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell metabolism, 8, 517-531 [PubMed]
Baschant U, Tuckermann J (2010). The role of the glucocorticoid receptor in inflammation and immunity.
J Steroid Biochem Mol Biol 120, 69-75 [PubMed]
Chichelnitskiy E, Vegiopoulos A, Berriel Diaz M, Ziegler A, Kleiman A, Rauch A, Tuckermann J, Herzig S (2009). In vivo PEPCK promoter mapping identifies disrupted hormonal synergism as a target of inflammation during sepsis in mice. Hepatology 50, 1963-71 [PubMed]
Tuckermann J, Kleiman A, Moriggl R, Spanbroek R, Neumann A, Illing A, Clausen BE, Stride B, Förster I, Habenicht AJ, Reichardt HM, Tronche F, Schmid W, Schütz G (2007). Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J Clin Invest. 117, 1381-1390 [PubMed]

Last update: May 31, 2010

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