Paracrine control of adrenal cortex on chromaffin cells proliferation

Objectives: Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on neurogenesis, neuronal survival and neuronal stem cells proliferation. The DHEA-producing adrenocortical cells and the adrenomedullary chromaffin cells are tightly intermingled and provide ample contact surfaces for paracrine interactions. 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 the effect of DHEA on bovine chromaffin cells proliferation induced by various growth factors and cytokines.

Methods: Chromaffin cells were isolated from young or adult bovines and then stimulated with graded concentrations of various growth factors with or without corticosteroid in serum-free medium. After 4 days incubation, proliferation was quantified using a MTS tetrazolium assay.

Results: Graded concentrations of LIF induced proliferation of chromaffin cells from young animals whereas EGF had no effect. On the contrary, EGF increased the cell proliferation in cells from adult animals, and LIF had no effect. In both kinds of cells, DHEA, as well as dexamethasone, decreased the proliferative effect induced by the growth factors suggesting that DHEA interacts with the glucocorticoid receptor. Surprisingly, DHEAS, the sulfate ester of DHEA, at high concentration, potentiated the effect of the growth factors only in cells from adult animals.

Conclusion: These data suggest that the sensitivity of bovine chromaffin cells to growth factors is age-dependent. In addition, we show that adrenal androgens exert different functions in the control of growth of chromaffin cells. Furthermore, DHEA and DHEAS might probably interact with growth factors and exert a role in the control of tissue formation and adrenal tumorigenesis.