Cyclic AMP and arachidonic acid: a tale of two pathways

Increasing evidence in recent years has demonstrated the regulatory effects of arachidonic acid and its metabolites on steroid hormone production in various steroidogenic tissues. In trophic hormone-stimulated steroidogenesis, arachidonic acid is rapidly released from phospholipids. This release is dependent upon hormone-receptor interaction and inhibition of arachidonic acid release results in an inhibition of steroidogenesis. Several of the earlier studies indicated that arachidonic acid acts at the rate-limiting step of steroid biosynthesis, the transfer of substrate cholesterol to the inner mitochondrial membrane, but the manner in which this occurred was not clear. Recently it has been demonstrated that arachidonic acid release can participate in the regulation of gene expression of the steroidogenic acute regulatory (StAR) protein which mediates cholesterol transfer to the inner mitochondrial membrane. These studies suggest that this fatty acid may be instrumental in transducing a signal from trophic hormone/receptor interaction to the nucleus utilizing a pathway different from the reported cyclic AMP pathway. It is possible that these two pathways cooperate and serve to co-regulate transcription factors, resulting in StAR gene expression and subsequent steroid production. This hypothesis may serve to explain and co-ordinate previous observations on the roles of cyclic AMP (cAMP) and arachidonic acid in steroid hormone biosynthesis.