Signal transduction involving cyclic AMP-dependent and cyclic AMP-independent mechanisms in the control of steroidogenesis.

The control of steroidogenesis via signal transduction mechanisms involving cAMP-dependent and cAMP-independent mechanisms is reviewed. Several structurally unrelated factors that are potent stimulators of steroidogenesis whose actions do not require cAMP and/or synthesis of proteins have been identified. These include various interleukins, a lipophilic factor from macrophages, a steroidogenic inducing protein from follicular fluid and an imidazole compound, calmidazolium. All of these factors are capable of inducing maximum steroidogenesis. Calcium is required for steroidogenesis in all steroidogenic cells. With the exception of the effects of angiotensin II, there is little evidence for a role of IP3 in the stimulation of the release of calcium from intracellular stores in steroidogenic cells under physiological conditions. There may however, be a cAMP-mediated activation of a plasma membrane calcium channel. Chloride channels that can be regulated by cAMP-dependent and -independent mechanisms, are present in steroidogenic cells. Chloride ions exert a negative effect on steroidogenesis because exclusion of chloride from the extracellular medium markedly enhances cAMP-stimulated steroidogenesis. Arachidonic acid and its lipoxygenase products are involved in the control of steroidogenesis via cAMP mediated processes. An arachidonic acid related thioesterase has been isolated that is activated by ACTH and which may be involved in the release of arachidonic acid. It is concluded that while cAMP is a second messenger for LH/ACTH in the control of steroidogenesis, other signalling systems exist which are potentially equally effective in controlling steroidogenesis. In addition, the action of cAMP requires other signalling pathways involving calcium and chloride ions, as well as arachidonic acid and its lipoxygenase products.