Dr. Christian G. Ziegler
Intraadrenale Role of DHEA in the development and tumorigenesis of the adrenal gland
In the adrenal gland steroid-producing cells of the adrenal cortex are in direct contact to the neural crest-derived catecholamine-producing chromaffin cells. Thus, the most important adrenocortical androgen, dehydroepiandrosterone (DHEA), produced in the inner zone of the adrenal cortex, might influence these chromaffin cells, especially the progenitor cells. Furthermore, DHEA has recently been identified as a crucial regulator in neural stem cell proliferation. DHEA might thus exert a hitherto unknown intra-adrenal function in the formation of adrenal tissue and tumorigenesis.
1. Primary culture of chromaffin cells and PC12 tumor cell line model:
Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on neurogenesis, neuronal survival and neuronal stem cells proliferation. The DHEA-producing adrenocortical zona reticularis cells and the adrenomedullary chromaffin cells are tightly intermingled and provide ample contact surfaces for paracrine interactions. Using primary bovine chromaffin cell cultures and the well-established PC12 cell line, as an ideal in vitro model for the study of chromaffin cells, me and my colleagues are trying to elucidate the effects of DHEA and various growth factors on the proliferation, morphology and signalling pathways of these cells. Employing immunohistochemistry, Western blotting and ELISA we especially focus on the proliferation, differentiation and important signalling pathways of chromaffin cells under the influence of DHEA.
2. Co-culture system and adrenal transplant model:
Besides this we are setting up co-cultures of chromaffin progenitor cells with normal adrenocotical cells or with adrenal androgen producing cells, to evaluate the molecular basis of the cellular crosstalk between these important cell populations of the adrenal gland. Furthermore, in order to analyse the development and regeneration of adrenal tissue we are planning to co-transplant chromaffin precursor cells and adrenocortical cells in vivo.
Future prospects and goals
Based on the in vitro and in vivo systems we hope to get insight in the role of DHEA in neuroendocrine cell development, the characteristics of tissue function, regeneration and its clinical impact on common disorders like hyperandrogenism.
- What is the effect of DHEA in the proliferation and differentiation of the primary chromaffin cells and in the PC12 cell model?
- What kind of cellular crosstalk exists between chromaffin cells and the adrenocortical cells in the formation and regeneration of adrenal tissue?
- How can we translate our findings in the clinic to develop new medical strategies to fight frequent disorders like hyperandrogenism
1998: master in biology at the department of Human Genetics, University of Würzburg
1999-2003: PhD student at the department of Human Genetics, University of Würzburg
2003-2004: Postdoc position in the department of Physiological chemistry I and Dermatology, University of Würzburg
since November 2004: Postdoc position at the TU Dresden, in the group of Prof. Dr. S.R. Bornstein; scientific area: molecular endocrinology