Pathogenesis of Corticotropic Tumors

Abstract

Subcellular molecular mechanisms underlying ACTH-secreting pituitary adenomas remain elusive. Genetic and acquired animal and cell models have provided insights into corticotroph cell tumorigenesis, including cell cycle abnormalities and aberrant glucocorticoid feedback mechanisms. Novel peptide therapies targeting somatostatin and/or dopamine (D-2) receptors and emerging microRNA studies may shed light on additional cellular pathways that regulate tumoral corticotroph cell function. Studying human pituitary corticotroph tumor biology is challenging. The rarity of the disease, as well as the small tumor size and commonly encountered specimen contamination with adjacent ``normal{''} pituitary tissue, all represent obstacles to studying disease mechanisms. Moreover, the lack of normal/non-autopsy derived human pituitary tissue and the inability to separate pure populations of viable corticotroph cells in primary non-human pituitary cultures does not enable easy comparison between normal and abnormal corticotroph cells. Therefore, despite technological and biological advances improving our knowledge of Cushing's disease, the pathophysiology of pituitary corticotroph adenomas remains unclear. This chapter focuses on accumulating knowledge, emphasizing recent progress in identifying molecular and genetic mechanisms contributing to the pathogenesis of Cushing's disease.