Molecular Biology of Cushing’s Disease

Abstract The proximal molecular pathogenesis of ACTH-secreting pituitary adenomas remains enigmatic. Several transgenic mice models have contributed important knowledge to understanding human pituitary disease; animal and cell models have provided novel insights into mechanisms underlying the pathogenesis of ACTH-secreting pituitary adenomas, mostly due to cell cycle disruption. Defective glucocorticoid feedback mechanisms also likely lead to enhanced POMC expression and corticotroph proliferation. Novel peptide therapies targeting somatostatin and/or dopamine (D2) receptors may also provide further insights into ACTH-secreting pituitary tumor pathogenesis. Studies investigating microRNA expression in pituitary corticotroph adenomas point to important functions of a unique class of gene regulators in the molecular biology of Cushing’s disease. Continuing research advancement will lead to better understanding of Cushing’s disease and development of novel therapeutic approaches.