title: Multifunctional cells in human pituitary adenomas: implications for paradoxical secretion and tumorigenesis.
abstract: Pituitary adenomas are very common in humans. They are of monoclonal origin, very heterogeneous, and produce frequently paradoxical secretion. The normal anterior pituitary (AP) contains some unorthodox multifunctional cells able to store more than one AP hormone (polyhormonal) and/or to express multiple hypothalamic-releasing hormone receptors (multiresponsive). Multifunctional AP cells seem to be involved in plasticity processes such as transdifferentiation or paradoxical secretion. Here, we have characterized the single-cell phenotypes of 15 human pituitary tumors, including prolactinomas, nonfunctioning adenomas, and adenomas from multiple endocrine neoplasia type I (MEN-I) and pituitary Cushing's disease patients. Individual tumor cells were typed according to expression of AP hormones and hypothalamic-releasing hormone receptors by combination of calcium imaging and multiple sequential immunocytochemistry in the same cells. We found a large heterogeneity among the different tumors. In eight of the 15 tumors studied, more than 80% of the cells presented a multifunctional phenotype. This may explain the occurrence of paradoxical secretion. In addition, our results suggest that human pituitary adenomas might derive from multifunctional cells. This is consistent with the existence of a link between pituitary plasticity and tumorigenesis.
authors.affiliation: Instituto de Biología y Genética Molecular, Department Fisiología, Facultad de Medicina, Ramón y Cajal 7, E-47005 Valladolid, Spain. carlosv@ibgm.uva.es
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.forename: Lucía
authors.initials: L
authors.lastname: Núñez
authors.forename: José M
authors.initials: JM
authors.lastname: de Campos
authors.forename: Daniel A
authors.initials: DA
authors.lastname: de Luis
authors.forename: Enrique
authors.initials: E
authors.lastname: Romero
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez
authors.forename: Javier
authors.initials: J
authors.lastname: García-Sancho
authors.forename: Carlos
authors.initials: C
authors.lastname: Villalobos
mesh_terms: D000236:Adenoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D003480:Cushing Syndrome / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015175:Prolactinoma / Q000378:metabolism / Q000473:pathology; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000032:analysis*
chemical_list: D010908:Pituitary Hormones, Anterior; D018017:Receptors, Pituitary Hormone-Regulating Hormone