Stefan R. Bornstein Intercellular crosstalk in the endocrine system
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Previous and current research
The unravelling of the human genome and proteome opens new avenues for defining
the complex cellular interactions of the neuroendocrine and immune system, and
its relevance for disease. Research in our laboratory is focused on two major
topics:1. Defining basic mechanisms and clinical implications of cellular crosstalk in endocrine tissues. We analyze, in a comprehensive manner, the components and mechanisms of this cellular crosstalk by defining the involved receptors, signalling pathways, transcription factors and gene expression profiles. Using the adrenal gland as a model we have demonstrated that tissue integrity, input from the nervous system or intercellular communication is essential for the normal functioning of the gland and the adequate respond to the homeostatic challenges of stress. We have demonstrated that intact intraglandular cellular interactions are required for normal development, differentiation and zonation of the adrenals and that alterations in intercellular communication, local production of neuropeptides, growth factors and cytokines, and aberrant expression of ectopic receptors are implicated in adrenal hyperplasia, autonomic hormone production and tumour formation.
2. Overweight and obesity are increasing at an alarming rate worldwide, reaching alarming epidemic proportion in the westernized world. Obesity is the major risk factor for lipid abnormalities, atherosclerosis, high blood pressure, diabetes mellitus type II and certain types of cancer. It is well established now that adipose tissue, besides its role in the deposition and release of fatty acids, is a highly active endocrine organ. We are interested in this endocrine function of adipose tissue and its involvement in the development of obesity associated diseases, especially the influence on the stress system, myocardiocytes and pancreatic beta-cells. In this context we could recently show a new direct influence of adipocytes on aldosterone secretion. This defines a new direct casual link between obesity and high blood pressure. We are now in the process of characterizing the responsible factors (adipotensins).
Future prospects and goals
Based on our previous findings we will use integrated approaches in both research areas using a wide array of techniques. This is a logical consequence of our previous work and a translation of basic science into clinical medicine.
How
does cellular crosstalk translate into differential intercellular signalling,
transcriptional regulation and gene expression?
How is cellular crosstalk
reflected in the process of development?
What can we learn from transgenic
animal models?
New therapeutic strategies
based on a thorough understanding of this form of integrative medicine.
Selected publications
Merke DP, Chrousos GP, Eisenhofer G, Weise M, Keil MF, Rogol AD, Van Wyk JJ, Bornstein SR (2000): Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency. N Engl J Med. 343:1362-1368.Galon J, Franchimont D, Hiroi N, Frey G, Boettner A, Ehrhart-Bornstein M, O'Shea JJ, Chrousos GP, Bornstein SR (2002): Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. FASEB J. 16:61-71.
Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg HS, Barthel A, Hauner H, McCann SM, Scherbaum WA, Bornstein SR (2003): Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci U S A. 100:14211-14216.
Bornstein SR, Yoshida-Hiroi M, Sotiriou S, Levine M, Hartwig HG, Nussbaum RL, Eisenhofer G. (2003): Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2). FASEB J. 17:1928-1930.
Bornstein SR, Zacharowski P, Schumann RR, Barthel A, Tran N, Papewalis C, Rettori V, McCann SM, Schulze-Osthoff K, Scherbaum WA, Tarnow J, Zacharowski K. (2004): Impaired adrenal stress response in Toll-like receptor 2-deficient mice. Proc Natl Acad Sci U S A. 101:16695-16700.
Stefan R. Bornstein
1988: MD at the University of Ulm
1988-1994: Resident and fellow at the Clinic of Internal Medicine, University of Ulm
1994-1997: Senior physician at the Clinic of Internal Medicine, University of Leipzig
1996-1999: Heisenberg-Scholarship of the German Research Society (DFG)
1997-2001: Research fellow and Unit chief at the Endocrine Branch, NICHD, National Institutes of Health, Bethesda, USA
2001-2004: Professor and Vice-Chair at the Department of Endocrinology and Metabolism, University of Düsseldorf
since 2004: Director, Medical Clinic III, University Clinic of Dresden
