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Front Oncol. 2015 Jun 09;5:124. doi: 10.3389/fonc.2015.00124. eCollection 2015.

Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.

Frontiers in oncology

Laura Senovilla, Lucía Núñez, José María de Campos, Daniel A de Luis, Enrique Romero, Javier García-Sancho, Carlos Villalobos

Affiliations

  1. Instituto de Biología y Genética Molecular (IBGM), CSIC , Valladolid , Spain.
  2. Instituto de Biología y Genética Molecular (IBGM), CSIC , Valladolid , Spain ; Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid , Valladolid , Spain.
  3. Hospital Universitario Del Río Hortega (HURH) , Valladolid , Spain.
  4. Departamento de Endocrinología y Nutrición, Hospital Clínico Universitario e Instituto de Endocrinología y Nutrición, Universidad de Valladolid , Valladolid , Spain.

PMID: 26106585 PMCID: PMC4460876 DOI: 10.3389/fonc.2015.00124

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.

Keywords: GHomas; calcium imaging; hypothalamic releasing factors; non-functioning pituitary adenomas; pituitary adenomas; somatotropinomas

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