Molecular determinants of pituitary cytodifferentiation.
The pituitary is a complex gland and is composed of several cell types, each responsible for the production of specific hormones. In the past, it was thought that one cell could make only one hormone; the concept of plurihormonality was poorly understood. Plurihormonal adenomas were thought to be either composed of multiple cell types, each producing one hormone (plurimorphous adenomas) or composed of poorly differentiated cells that exhibited abnormal production of multiple hormones. However, the molecular factors that determine hormone production have now been identified as transcription factors that target specific hormone genes. These factors have clarified three main pathways of cell differentiation. ACTH-producing corticotrophs are determined by corticotropin upstream transcription-binding element (CUTE) proteins including neuroD1/beta 2. Bihormonal gonadotrophs require expression of steroidgenic factor (SF)-1. The complex family of Pit-1 expressing cells can mature into somatotrophs, mammosomatotrophs, lactotrophs or thyrotrophs with the additional expression of estrogen receptor (ER) alpha, which enhances PRL secretion, or thyrotroph embryonic factor (TEF) which stimulates TSH-beta production. The recognition of these molecular determinants of adenohypophysial cytodifferentiation has clarified the patterns of plurihormonality which have been recognized in pituitary adenomas and provide a framework for classification of these tumors.
Asa
S L
SL
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Ezzat
S
S
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D008954:Models, Biological; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology; D010907:Pituitary Hormones / Q000096:biosynthesis; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D054339:Steroidogenic Factor 1; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D054339:Steroidogenic Factor 1; C489490:TEF protein, human; C489491:Tef protein, mouse; D050817:Transcription Factor Pit-1; D014157:Transcription Factors