Sympathetic effects on the steroidogenesis and proliferation of adrenocortical cells in vitro

Recent evidence supports the hypothesis that sympathetic neurons play a significant role in the regulation of adrenocortical cell proliferation and steroidogenesis. Co-cultures of rat adrenocortical and sympathetic ganglion cells have been established to study sympatho-adrenal interactions. In these studies we have compared differentiation, growth and secretion of adrenocortical cells grown in co-culture with those grown alone. Adrenocortical cells were identified using 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) histochemistry or immunocytochemistry; sympathetic neurons were identified using immunocytochemical localization of tyrosine hydroxylase. The sympathetic neurons usually form clusters of 3-10 cells, and extend neurites to adrenocortical cells. Adrenocortical cells continue to proliferate, express 3 beta HSD and sequester lipid droplets. In the co-cultures, the adrenocortical cells are smaller, form larger clusters and show denser 3 beta HSD staining than the adrenocortical cells alone. The presence of the sympathetic neurons enhances adrenocortical cell proliferation as shown by a 2 fold increase in the number of 3 beta HSD(+) cells as well as increased BrdU incorporation after 48 hrs. Steroidogenesis appeared to be enhanced in the presence of sympathetic neurons as demonstrated by 3 beta HSD(+) staining and a 2-fold greater corticosterone and aldosterone secretion. However, when secretion is expressed per number of adrenocortical cells, the rates are comparable, indicating that secretion rate per cell remains unaltered by the presence of neurons. The effects of sympathetic neuron activation on adrenocortical cells remain to be determined.