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Dehydroepiandrosterone-sulphate (DHEA-S) promotes neuroendocrine differentiation of chromaffin pheochromocytoma PC12 cells.

Abstract：

:The major source for dehydroepiandrosterone (DHEA) and its sulphate compound DHEA-S is the inner zone of the adrenal cortex, which is in direct contact to adrenomedullary chromaffin cells. Due to their close proximity, direct interactions of DHEA and DHEA-S with chromaffin cells during adrenal gland development and throughout the whole life span are hypothesized. A possible direct effect of DHEA-S and the cellular and molecular mechanisms of DHEA-S action on chromaffin cells remain unresolved. Therefore, in this study, we aimed at clarifying DHEA-S effects and mechanisms of action on rat chromaffin PC12 cells. DHEA-S (10(-6)mol/l) inhibited nerve growth factor (NGF, 20ng/ml)-induced cell proliferation by 66% (n=4, p<0.001). In NGF-stimulated cells, neuronal differentiation was inhibited by DHEA-S, as demonstrated by a 22% reduction (n=3; p<0.05) of neuronal differentiation marker expression, synaptosome-associated protein of 25kDa (SNAP-25), and a 59% (n=6; p<0.001) decrease in neurite outgrowth. Moreover, DHEA-S stimulated expression of endocrine marker chromogranin A (CgA) by 31% (n=4; p<0.05 vs. control) and catecholamine release from NGF-treated PC12 cells by 229% (n=3-5; p<0.001), indicating a DHEA-S-induced shift towards neuroendocrine differentiation. On a molecular level, DHEA-S diminished NGF-induced ERK1/2 phosphorylation. Taken together, DHEA-S inhibited NGF-induced proliferation and neuronal differentiation and shifted cells towards a more endocrine phenotype. Interference of DHEA-S with NGF-stimulated ERK1/2 activation might be involved in this effect. Our study provides support for the notion that adrenocortical-derived DHEA-S impacts adrenomedullary chromaffin cells during development and differentiation.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Krug AW,Langbein H,Ziegler CG,Bornstein SR,Eisenhofer G,Ehrhart-Bornstein M

doi

10.1016/j.mce.2008.10.026

subject

Has Abstract

pub_date

2009-03-05 00:00:00

pages

126-31

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(08)00501-7

journal_volume

300

pub_type

杂志文章

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Dehydroepiandrosterone-sulphate (DHEA-S) promotes neuroendocrine differentiation of chromaffin pheochromocytoma PC12 cells.