Transgenic and Knockout Mouse Models Clarify Pituitary Development, Function and Disease

Abstract

Mouse models have been used to study various aspects of pituitary development, function and disease. Transgenic or knockout technology has been applied to examine the regulation of hormone gene expression and the pathophysiology of its alterations, to ascertain the factors that determine cell differentiation, and to manipulate oncogenesis. Transgenic mice have elucidated the necessary elements required for the tissue- and cell-specific expression of pituitary hormones. Transgenic and knockout technologies have derived mice with hormone overexpression or abrogation of hormone action, and have identified novel hormones. The role of precursor cells in cell differentiation has been confirmed by genetic ablation of cell lineages. Inactivation of transcription factors implicated in pituitary organogenesis and cytogenesis has proven their critical roles in pituitary development. Pituitary oncogenesis has been studied by promoter-directed oncogene expression or tumor suppressor gene ablation, by adenohypophysiotropic hormone overexpression, or by growth factor or receptor overexpression. The tumors have provided a number of cell lines for use in the continuing study of pituitary physiology and pathology. These models may also be used in the future to examine novel therapeutic strategies for the management of patients with pituitary disorders.