The adrenal cortex produces
steroid hormones as adrenocortical
hormones in the body, secreting
mineralocorticoids,
glucocorticoids, and adrenal
androgens, which are all considered essential for life. Adrenocortical
tumors harbor divergent hormonal activity, frequently with
steroid excess, and disrupt homeostasis of the body.
Aldosterone-producing
adenomas (APAs) cause primary
aldosteronism (PA), and
cortisol-producing
adenomas (CPAs) are the primary cause of
Cushing's syndrome. In addition,
adrenocortical carcinoma (ACC) is a highly malignant
cancer harboring poor prognosis. Various genetic abnormalities have been reported, which are associated with possible pathogenesis by the alteration of intracellular signaling and activation of
transcription factors. In particular, somatic mutations in APAs have been detected in genes encoding
membrane proteins, especially
ion channels, resulting in hypersecretion of
aldosterone due to activation of intracellular calcium signaling. In addition, somatic mutations have been detected in those encoding cAMP-PKA signaling-related factors, resulting in hypersecretion of
cortisol due to its driven status in CPAs. In ACC, mutations in tumor suppressor genes and Wnt-β-
catenin signaling-related factors have been implicated in its pathogenesis. In this article, we review recent findings on the genetic characteristics and regulation of intracellular signaling and
transcription factors in individual
tumors.