Pituitary Trophic Status as a Tumorigenic Determinant

Abstract

Pituitary tumors are commonly encountered benign adenomas. Pituitary cell trophic status is an important determinant of pituitary adenoma development. Hormone secreting anterior pituitary cells exhibit slow turnover rates. Subsequent postnatal alterations in pituitary size are determined throughout the lifespan by both extrinsic and intrinsic factors. PTTG, a mammalian securin protein is overexpressed in several endocrine (pituitary, thyroid, breast) tumors, promotes pituitary cell proliferation, and is also a powerful transforming gene. Senescence, or proliferative arrest can be triggered by aneuploidy or DNA-damage, and Pttg deficiency triggers pituitary cell proliferation arrest, aneuploidy and DNA damage pathway. We hypothesize that pituitary senescence accounts for the overwhelming predominance of benign vs. malignant pituitary tumors, and here we present evidence favoring this hypothesis derived from the Pttg-null mouse.