Protein Kinase A Signaling in Cortisol Production and Adrenal Cushing’s Syndrome

The adenosine 3',5'-cyclic monophosphate-protein kinase A (cAMP-PKA) signaling pathway is highly utilized in human physiology. It is a crucial component of development and is vital to cellular function in nearly all tissues. Indeed, genetic mutations to cAMP-PKA machinery are found in many pathologies, including multiple cancers, cardiac myxoma, neurodevelopmental disorders, and hypercortisolism. Cyclic AMP and PKA were first identified as vital components in cortisol synthesis over 50 years ago, yet the cellular mechanisms connecting PKA to cortisol production are still not well understood. This article will review evidence for PKA's roles in adrenal gland zona fasciculata steroidogenesis and consider recent studies of the stress hormone disease adrenal Cushing's syndrome to synthesize a current model for cAMP-PKA actions in cortisol production.