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Understanding the systemic consequences of disrupted steroidogenesis

Applicant Dr. Nils Krone
Subject Area Pediatric and Adolescent Medicine
Term from 2017 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 329397225
 
Final Report Year 2023

Final Report Abstract

Overall, this project has led to several well-recognised outputs that have been well published in leading scientific journals. Furthermore, within this project, we have defined crucial steps in steroid hormone endocrinology in zebrafish and has helped to firmly establish zebrafish as basic and translational research model in steroid endocrinology. We have laid the scientific foundations to understand the differential role steroid hormones in sex development and metabolism in zebrafish. Furthermore, this project has helped us to answer questions linking translational questions about the interaction of steroid hormones with crucial pathways facilitating metabolism and homeostasis. In addition, we have been able to provide novel insights into the regulatory interplay of glucocorticoids with metabolic pathways and central nervous processes. Despite the fact that we have answered several exciting research questions, we have also made several observations that have to our knowledge not been published so far and warrant future studies. These include that glucocorticoid deficiency in unstressed organisms appears to be compatible with life, which has in the meanwhile also been observed by other groups in zebrafish as well as in mice, rats and xenopus models of glucocorticoid deficiency. Furthermore, we believe that our observations about metabolic phenotypes in glucocorticoid deficient and resistant animal that are very similar phenotypes one might expect in glucocorticoid excess warrant further investigations and might even lead to paradigm shift about the role of glucocorticoids in the future. Such observations have not only relevance to questions in basic science, but we also anticipate that there might be translational relevance for individuals with inborn errors of steroidogenesis. lt is well recognised that people with non-adherence to glucocorticoid survive during unstressed situations in life, but the long-term consequence of intermitted glucocorticoid deficiency remain elusive. We believe that our result will be useful for the future design of translational research studies using model systems and potentially in humans.

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