Benutzerspezifische Werkzeuge

Conceptual innovation and coherence

A better understanding of the mechanisms and pathophysiology of adrenal dysregulation is crucial to improve the diagnosis, clinical management and survival of patients with adrenal disorders involving hyper- or hypofunction of cortical or medullary adrenal components. This requires consideration of the adrenal microenvironment and can benefit from a multidisciplinary approach of basic and clinical scientists, including endocrinologists, clinical chemists, immunologists, intensivists, pharmacologists, geneticists, pathologists and vascular biologists. This microenvironment is unique in several ways: (i) it comprises two independent but closely interacting endocrine systems, the adrenocortical steroid-producing system and the adrenomedullary catecholamine-producing system; (ii) it harbours multipotent progenitor and stem cells; (iii) it is highly vascularised with endothelial cells in spatial and functional crosstalk with the two endocrine systems; (iv) it is a tissue with high antioxidative capacity; and (v) it represents a recruitment site of leukocytes during inflammation (Fig.1).

 Introduction fig 1

Figure:Adrenal microenvironment with its different cell types: the interactions thereof are important mechanistic components during adrenal (dys)function. Participating research groups have complementary expertise in each of the cellular compartments and form an established team of adrenal researchers with long-standing collaborations.

While previous studies have focused on adrenal cells as complete endocrine systems, our approach is to integrate this with studies of other distinct cellular components of the adrenal microenvironment, taking into consideration the intimate regulatory crosstalk between endocrine and non-endocrine cells. This innovative approach for examining the complete adrenal microenvironment will provide an improved basis for understanding adrenal-related pathophysiology, and thereby set the groundwork for establishing improved diagnosis, clinical care and treatment of adrenal disorders and associated diseases.

An interdisciplinary team approach merging basic and clinical scientists united in one campus is an important requirement for the successful implementation of this research proposal. Together, the research unit will provide a comprehensive platform involving appropriate cellular and animal model systems (e.g. genetically modified mice including adrenocortical-specific or sympathoadrenal-specific conditional knockout mice), state-of-the-art analytical tools and clinical protocols associated with biobanks linked to prospectively collected patient data. The conceptual innovation of this approach has ramifications that extend beyond adrenal-specific diseases to more common clinical disorders.