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1 Instituto de Biologia y Genetica Molecular and Departamento de Fisiologia y Bioquimica, Universidad de Valladolid and Consejo Superior de Investigaciones Cientificas, Valladolid, Valladolid, Spain
* To whom correspondence should be addressed. E-mail: jgsancho{at}ibgm.uva.es.
Anterior pituitary (AP) contains some unorthodox multifunctional cells that store and secrete two different AP hormones (polyhormonal cells) and/or respond to several hypothalamic releasing hormones (HRHs) (multiresponsive cells). Multifunctional cells may be involved in paradoxical secretion (secretion of a given AP hormone evoked by a non-corresponding HRH) and trans-differentiation (phenotypic switch between different mature cell types without cell division). Here we combine calcium imaging (to assess responses to the four HRHs) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of thyrotropes in normal male and female mice. Surprisingly, most of the thyrotropes were polyhormonal, containing, in addition to TSH, LH (40-42%) and prolactin (19-21%). Thyrotropes co-storing GH and/or ACTH were found only in females (24% of each type). These results suggest that co-storage of the different hormones does not happen at random and that gender favors certain hormone combinations. Our results indicate that thyrotropes are a mosaic of cell phenotypes rather than a single cell type. The striking promiscuity of TSH storage should originate considerable mix-up of AP hormone secretions on stimulation of thyrotropes. However, response to TRH was much weaker in the polyhormonal thyrotropes than in the monohormonal ones. This would limit the appearance of paradoxical secretion under physiological conditions and suggests that timing of hormone and HRH receptors expression during the transdifferentiation process are finely and differentially regulated.
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