Pituitary

Abstract

In the last decade, a number of regulatory proteins have been shown to be important in the development and function of the pituitary gland. These transcription factors act at different stages of development to trigger the expression of specific genes that regulate the development of specific cell lineages, as well as the expression of hormone genes. Indeed, over the last year, several interesting articles in this challenging new area have been extremely helpful for understanding pituitary gland genetics and pathology, as well as the physiology of anterior pituitary hormonal regulation. Other selections should have important clinical implications for practicing physicians. The resulting summary will hopefully provide valuable help for updating busy pediatric endocrinologists on the most interesting and relevant work recently published in the field of pituitary studies and will furnish insights into future directions. Mechanism of the year PROP-1 mutations: transition from hyperplasia to hypoplasia Role of PROP-1 in pituitary gland growthWard RD, Raetzman LT, Suh H, Stone BM, Nasonkin IO, Camper SA Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Mich., USA Mol Endocrinol 2005;19:698-710 Background: The PROP-1 gene is a tissue-specific, paired-like, homeodomain transcription factor expressed early in the anterior pituitary. The Prop-1 gene plays an essential role in the evolution of pituitary cells secreting GH, PRL, TSH and gonadotropins, as shown by hormone deficiencies in subjects with PROP-1 mutations. ACTH deficiency seems to be more common than was formerly thought. Pituitary morphology in patients carrying PROP-1 mutation varies considerably between small, normal and up to an extremely enlarged pituitary gland size, with no abnormalities among pituitary stalk and posterior pituitary. Spontaneous mutant Ames dwarf mice, however, display pituitary hypoplasia. The mechanism whereby PROP-1 regulates anterior pituitary growth from pituitary hyperplasia to hypoplasia is still largely unclear. Methods: Longitudinal studies in normal and Prop-1-deficient generated mice were carried out from early embryogenesis to adulthood. The volume of Rathke's pouch and its derivatives, the position and number of dividing cells and the rate of apoptosis and cell migration were evaluated. Results: Prop-1 deficiency results in early abnormal expansion of both Rathke's pouch and of the lumen with late pituitary dysmorphology and severe hypoplasia. Volumetric analysis by three-dimensional reconstruction confirms pituitary growth pattern with tenfold pituitary volume reduction after birth. The volumetric measurements suggest that proliferating cells progressively fail to populate the anterior pituitary, while pulse chase labeling shows impairment of the migration pattern of progenitors from the perilumenal region to the anterior lobe. After birth, mutant pituitaries displayed increased apoptosis. Conclusion: Mutations in the transcription factor Prop-1 causes dysmorphic pituitary primordium, ...