Genetic defects in the development and function of the anterior pituitary gland

Abstract

Genetic defects affecting the hypothalamic-pituitary-target organ axes can cause a variety of diseases involving restricted or broad disruptions of human development and physiology. At the level of the anterior pituitary gland, mutations in the genes encoding key transcription factors, hypothalamic releasing and inhibiting hormone receptors, and the pituitary hormones themselves, can all result in the loss of action of one or more of the specialized hormone-secreting cell types. This article focuses on the effects of inherited and sporadic mutations on the development and function of the anterior pituitary. Mutations in the genes encoding the HESX1, PITX2, LHX3, LHX4, PROP1, PIT1, SF1, and TPIT developmental transcription factors are associated with combined pituitary hormone deficiency diseases. By contrast, deleterious alterations in the genes that encode hypothalamic releasing hormone receptors or pituitary hormones, such as the growth hormone releasing hormone receptor or growth hormone genes, usually result in phenotypes that reflect specific defects in the hormone-secreting capacities of individual anterior pituitary cell types.