Differentiation of chromaffin progenitor cells: Possible role of DHEA and DHEAS

Abstract

Dehydroepiandrosterone (DHEA) and its sulfated form DHEAS are the most abundant hormones in the human body. They are secreted by the inner adrenocortical zone which is in direct contact with the adrenal medulla. It has been suggested that DHEA has effects on the neurogenesis and the maintenance of human neural stem cells. In addition, recent studies have shown that glucocorticoids are not essential for the formation of the neuroendocrine phenotype of chromaffin cells. The aim of present study was to investigate the potential role of DHEA and DHEAS on the development of chromaffin progenitor cells. Chromaffin progenitor cells were isolated in low-attachment conditions. These cells were able of self-renewal and grew into spheres from single cells. Chromaffin-spheres expressed neuronal progenitor markers such as nestin, synaptophysin and prominin, chromaffin markers such as TH and PNMT and neuronal markers such as vesicular transporter of acetylcholine. In order to define the niche required for chromaffin sphere development, the spheres were seeded using different coating (poly-D-lysine, collagen, and fibronectin) in the presence of growth factors (EGF, bFGF and LIF). We then induced their differentiation with various factors including DHEA, DHEAS, dexamethasone (Dex), nerve growth factor (NGF) and bone-morphogenetic-protein 4. DHEA as well as Dex induced the expression of PNMT mRNA on poly-D-lysine coated plates. In addition, the expression of nestin mRNA is strongly reduced by treatments with DHEAS on poly-D-lysine and with DHEA, DHEAS on fibronectin. In contrast, DHEAS caused a higher expression of nestin on collagen coated plates. In summary, we were able to isolate chromaffin progenitor cells. These cells were able to self renew and to differentiate. The combination of poly-D-lysine coating and growth factors seems to create an environment mimicking the niche needed for chromaffin cell progenitor's differentiation. In addition, these data indicate that DHEA and DHEAS might play a key role in chromaffin cell development.