title: Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.
abstract: Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs.
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), CSIC , Valladolid , Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), CSIC , Valladolid , Spain ; Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid , Valladolid , Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Núñez
authors.affiliation: Hospital Universitario Del Río Hortega (HURH) , Valladolid , Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: de Campos
authors.affiliation: Departamento de Endocrinología y Nutrición, Hospital Clínico Universitario e Instituto de Endocrinología y Nutrición, Universidad de Valladolid , Valladolid , Spain.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: de Luis
authors.affiliation: Departamento de Endocrinología y Nutrición, Hospital Clínico Universitario e Instituto de Endocrinología y Nutrición, Universidad de Valladolid , Valladolid , Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Romero
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), CSIC , Valladolid , Spain ; Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid , Valladolid , Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Sancho
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), CSIC , Valladolid , Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Villalobos
keywords: GHomas; calcium imaging; hypothalamic releasing factors; non-functioning pituitary adenomas; pituitary adenomas; somatotropinomas