The role of homeodomain transcription factors in heritable pituitary disease

Abstract

The anterior pituitary gland secretes hormones that regulate developmental and physiological processes, including growth, the stress response, metabolic status, reproduction and lactation. During embryogenesis, cellular determination and differentiation events establish specialized hormone-secreting cell types within the anterior pituitary gland. These developmental decisions are mediated in part by the actions of a cascade of transcription factors, many of which belong to the homeodomain class of DNA-binding proteins. The discovery of some of these regulatory proteins has facilitated genetic analyses of patients with hormone deficiencies. The findings of these studies reveal that congenital defects-ranging from isolated hormone deficiencies to combined pituitary hormone deficiency syndromes-are sometimes associated with mutations in the genes encoding pituitary-acting developmental transcription factors. The phenotypes of affected individuals and animal models have together provided useful insights into the biology of these transcription factors and have suggested new hypotheses for testing in the basic science laboratory. Here, we summarize the gene regulatory pathways that control anterior pituitary development, with emphasis on the role of the homeodomain transcription factors in normal pituitary organogenesis and heritable pituitary disease.