Molecular basis of pituitary dysfunction in mouse and human.

Abstract

The pituitary gland functions as an intermediary between the brain and the peripheral endocrine organs of the body (Tortora and Grabowski 1996). In the context of a complex system of feedback control, the pituitary gland relays signals from the hypothalamus to its target organs by secreting various hormones. These hormone signals, which are transmitted throughout the endocrine system, reflect the current homeostatic conditions of the body. Mechanisms of compensation, including the regulation of gene transcription, hormone secretion, and cell proliferation, allow the pituitary to respond to the continually changing needs of the organism. It is in this way that the pituitary aids in the regulation of many vital processes, including growth, metabolism, reproduction, and stress response. The mammalian pituitary is comprised of three lobes: the posterior lobe, the intermediate lobe, and the anterior lobe. The anterior lobe of the pituitary is composed of functionally distinct cell types that are the primary site of endocrine regulation. During embryogenesis, the anterior and intermediate lobes of the pituitary develop from an invagination in the oral ectoderm known as Rathke’s pouch (Dubois and ElAmraoui 1995). The pouch eventually separates from the oral ectoderm and undergoes a period of intense proliferation. This is followed by differentiation into the five anterior pituitary cell types on the rostral side of the pouch and the intermediate lobe melanotropes on the caudal side of the pouch (Dubois and Hemming 1991). By birth, the anterior pituitary is composed of functioning corticotropes, thyrotropes, somatotropes, gonadotropes, and lactotropes that produce adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), gonadotropins (FSH and LH), and prolactin (PRL), respectively. Expression of each hormone gene, which defines the terminal differentiation of each cell type, occurs in a spatially and temporally specific manner during pituitary organogenesis (Japon et al. 1994; Burrows et al. 1999). The mechanisms that control this process involve the secretion of signals from surrounding structures and the expression of a cascade of homeodomain transcription factors. Studies in both mouse and human reveal that control of signaling events and homeobox gene expression is essential for proper pituitary gland development (Watkins-Chow and Camper 1998; Dasen and Rosenfeld 1999). Deregulation of these events can lead to various forms of pituitary gland dysfunction, including hypopituitarism and adenomas.