Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 16 P25

ECE2008 Poster Presentations Adrenal (61 abstracts)

Dehydroepiandrosterone (DHEA) exerts a prominent effect on chromaffin PC12 cell differentiation processes

Christian G Ziegler , Heike Langbein , Vladimir Vukicevic , Stefan R Bornstein , Monika Ehrhart-Bornstein & Alexander W Krug


Medical Clinic III, Dresden, Germany.


Within the adrenal gland, chromaffin cells and their progenitors are exposed to a wide variety of growth factors and hormones, including adrenal androgens such as DHEA. The DHEA producing-zona reticularis of the adrenal cortex is in close proximity to the neural crest-derived catecholamine-producing chromaffin cells of the medulla, enabling strong paracrine interactions. In vivo studies in humans revealed that congenital adrenal hyperplasia due to 21-hydroxylase (OH) deficiency results in androgen excess accompanied by severe adrenomedullary dysplasia and chromaffin cell dysfunction. Based on this evidence our in vitro study now aimed at further elucidating the effect of DHEA on chromaffin PC12 cells on a molecular level, focussing on cell survival and differentiation processes.

We could show that DHEA significantly reduced nerve growth factor (NGF)-induced cell survival as well as neuronal markers, such as neurite outgrowth and expression of neuronal marker proteins, like SNAP-25 and VAMP-2. Accordingly, DHEA was found to stimulate the NGF-stimulated cells towards a more neuroendocrine phenotype. Thus, DHEA largely elevated catecholamine release from NGF-induced PC12 cells and enhanced expression of the neuroendocrine marker chromogranin A. In a next step, we explored the molecular mechanisms of DHEA and NGF interaction in more detail. We could further demonstrate that DHEA significantly reduced NGF-mediated ERK1/2 MAPK activation. Differentiation as well as proliferation processes in PC12 cells are accompanied by ERK 1/2 activation.

In summary, our data demonstrate that DHEA influences differentiation processes in PC12 pheochromocytoma cells. DHEA drives the cells in the presence, but not in the absence, of NGF towards a more neuroendocrine phenotype. Our studies further suggest that this effect might be due to interference of DHEA with NGF-induced ERK1/2 activation by a rapid, so called non-genomic signalling mechanism.

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