Project Details
Projekt
Sonic hedgehog signalling in different forms of adrenal hyperplasia
Subject Area
Endocrinology, Diabetology, Metabolism
Term
from 2011 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 189897882
The development of obesity and metabolic syndrome are intimately connected with changes in adrenal function. In the first funding period, we showed that diet-induced obesity increases synthesis and release of steroid hormones by the adrenal cortex. It does so by inducing cortical hyperplasia and activating transcription of steroidogenic enzymes. This is associated with increased Shh signaling in the adrenal capsule (the source of cortical progenitors). The goal in this funding period is to define transcriptional targets of the Shh pathway in the adrenal capsule, and to understand the functional requirement for Shh signalling in cortical hyperplasia induced by different mechanisms. The Shh pathway is regulated at many levels by lipoprotein and lipid metabolism. We will therefore investigate functional connections between disturbances in lipid metabolism, altered Shh signalling in the adrenal, and adrenal hyperplasia. This work outlined here will advance our understanding of the signalling circuitry underlying adrenal homeostasis, the molecular mechanisms contributing adrenal dysfunction and how the global metabolic state exerts local influences on adrenal function.
DFG Programme
Clinical Research Units
