Role of ornithine decarboxylase in granulosa-cell replication and steroidogenesis in vitro

We investigated the role of ornithine decarboxylase in ovarian steroidogenesis and granulosa-cell replication under basal and hormonestimulated conditions in vitro. Enzyme activity was markedly (>95 or >99%) reduced by DL-difluoromethyl-ornithine or 1,3-diaminopropane, which significantly impaired granulosa-cell replication in log-phase cultures. However, inhibition of ornithine decarboxylase activity augmented basal and hormonestimulated steroid production per cell, an effect abolished by cyanoketone, a specific inhibitor of steroid synthesis. Both the anti-proliferative and the steroidogenic effects of enzyme inhibition were substantially reversed by putrescine, the end-product of the reaction. Thus, ornithine decarboxylase, or polyamines, may be required for granulosa-cell replication, while deprivation of these compounds facilitates the expression of more differentiated cell function, such as steroid synthesis.