Sexual dimorphism of adrenal hormone action in metabolic tissues
Principal Investigators
Prof. Dr. rer. nat.
Stephan Herzig
Helmholtz Zentrum München (HMGU)
Institute for Diabetes and Cancer (IDC)
Endocrinology and Molecular Biology
stephan.herzig[at]helmholtz-muenchen.de
Prof. Dr. rer. nat.
Henriette Uhlenhaut
Helmholtz Zentrum München (HMGU)
Institute for Diabetes and Endocrinology (IDE)
Chair of Metabolic Programming
TUM School of Life Sciences Weihenstephan
ZIEL-Institute for Food & Health
Henriette.uhlenhaut[at]tum.de
Scientific Staff
Nina Henriette Uhlenhaut – PI
Celine Jouffe – Postdoc
Aikaterini Mechtidou – PhD
Project Description
Project A09 deals with the over-activation of adrenal function and glucocorticoid (GC) signaling which lead to severe metabolic complications. As major effectors of the adrenal gland, GCs are essential regulators of physiology and metabolism. GCs have been shown to affect males and females differently in both rodent studies and clinical settings. Our project aims to identify the molecular and epigenetic mechanisms underlying the sexually dimorphic response to adrenal steroids observed in rodents and humans. Using total RNASeq and ChIPseq profiling, we plan to identify metabolic GC-driven, sexually dimorphic regulators both at the miRNA and the transcription factor binding level. By modulating these identified effectors of the hypothalamic-pituitary-adrenal (HPA) axis, we hope to contribute to ameliorating symptoms of GC excess, which may be more pronounced or frequent in one sex.
Aims
(I) Define and functionally evaluate adrenal steroid-driven, sexually dimorphic microRNAs in adipose tissue
(II) Map genome-wide sex-specific chromatin binding by Glucocorticoid Receptor (GR) to identify co-regulators relaying adrenal signals
PhD/MD-Thesis:
Aikaterini Mechtidou: ‘Chromatin modifiers mediating genomic GR actions’; PhD thesis started fall 2017
Publications
Glantschnig C, Koenen M, Gil-Lozano M, Karbiener M, Pickrahn I, Williams-Dautovich J, Patel R, Cummins CL, Giroud M, Hartleben G, Vogl E, Blüher M, Tuckermann J, Uhlenhaut H, Herzig S, Scheideler M. A miR-29a-driven negative feedback loop regulates peripheral glucocorticoid receptor signaling. FASEB J. 2019; 33: 5924–41.
Glantschnig C, Mattijssen F, Vogl ES, Khan AA, Garcia MR, Fischer K, Müller T, Uhlenhaut H, Nawroth P, Scheideler M, Rose AJ, Pellegata N, Herzig S. The glucocorticoid receptor in brown adipocytes is dispensable for the systemic control of energy homeostasis through brown adipose tissue. EMBO Rep.
Rose AJ, Herzig S. Metabolic control through glucocorticoid hormones: An update. Mol. Cell. Endocrinol. 2013; 380: 65–78.