Genetic Regulation of Pituitary Gland Development in Human and Mouse

• Published in: Endocrine reviews Vol. 30; no. 7; pp. 790 - 829
• Main Authors: Kelberman, Daniel, Rizzoti, Karine, Lovell-Badge, Robin, Robinson, Iain C. A. F, Dattani, Mehul T
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.12.2009; Copyright by The Endocrine Society; The Endocrine Society
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - physiology; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Humans; Hypothalamus - embryology; Hypothalamus - physiology; Mice; Morphogenesis - genetics; Morphogenesis - physiology; Pituitary Gland - embryology; Pituitary Gland - physiology; Pituitary Hormones - genetics; Pituitary Hormones - physiology; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 0163-769X; 1945-7189
• DOI: 10.1210/er.2009-0008

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. This review describes the complex genetic cascade of signaling molecules and transcription factors implicated in murine and human hypothalamo-pituitary development, and the consequences of mutations within these in mouse and human.