Endocrine Abstracts (2006) 11 P755

Opposite effects of DHEA and DHEAS on chromaffin cells proliferation

F Sicard, AW Krug, CG Ziegler, S Sperber, M Ehrhart-Bornstein & SR Bornstein

Carl Gustav Carus University Medical School, Dresden, Germany.

Dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS are neurosteroids with potential effects on neurogenesis, neuronal survival and neuronal stem cells proliferation. DHEA is produced by the inner adrenocortical zone, which is in direct contact to the adrenomedullary chromaffin. Unlike the closely related sympathetic neurons, chromaffin cells are able to proliferate throughout the life span. The aim of the present study was to examine in vitro the effect of DHEA and DHEAS on bovine chromaffin cells proliferation induced by various growth factors and cytokines.

Graded concentrations of leukemia inhibitory factor (LIF) induced proliferation of chromaffin cells from young animals whereas epidermal growth factor (EGF) had no effect. On the contrary, EGF increased the cell proliferation in cells from adult animals, whereas LIF was inactive. In both cases, DHEA, as well as dexamethasone, decreased the proliferative effect induced by the growth factors. Neither DHEA nor dexamethasone did affect cell death. Surprisingly, DHEAS potentiated, in a dose-dependent-manner, the effect of growth factors on proliferation in cells from adult but not from young animals.

These data show that the sensitivity of bovine chromaffin cells to different growth factors is age-dependent. In addition, we show that the adrenal androgen DHEA and its sulphated form DHEAS can exert oposite functions in the control of chromaffin cell growth. Furthermore, DHEA and DHEAS probably interact with growth factor-induced proliferation and therefore exert a role in the control of adrenomedullary tissue formation. In summary, a differential regulation of adrenomedullary development with age-dependent differences in the sensitivity of these cells to growth factors and adrenal androgens is suggested.

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