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Rapid Changes in Anterior Pituitary Cell Phenotypes in Male and Female Mice after Acute Cold Stress

Instituto de Biología y Genética Molecular, Universidad de Valladolid and Consejo Superior de Investigaciones Científicas, Sanz y Forés s/n, 47003 Valladolid, Spain

Address all correspondence and requests for reprints to: Javier García-Sancho, Instituto de Biología y Genética Molecular, C/ Sanz y Forés s/n, 47003 Valladolid, Spain. E-mail: jgsancho{at}ibgm.uva.es.

The anterior pituitary (AP) is made of five different cell types. The relative abundance and phenotype of AP cells may change in different physiological situations as an expression of pituitary plasticity. Here, we analyze in detail the phenotype of mouse corticotropes and the effects of acute cold stress on AP cell populations. The hormone content and the expression of hypothalamic-releasing hormone (HRH) receptors in all the five AP cell types were studied in the male and female mice at rest and after a 30-min cold stress. Expression of HRH receptors was evidenced by imaging the single-cell cytosolic Ca²⁺ responses in fura-2-loaded cells. Hormone contents were studied by multiple, simultaneous immunofluorescence of all the five hormones. Corticotropes displayed a striking sexual dimorphism, even in the resting condition. Male corticotropes showed the orthodox phenotype. They were monohormonal, storing only ACTH, and monoreceptorial, responding only to CRH. In contrast, female corticotropes were made of about equal parts of orthodox cells and multifunctional cells, which co-stored additional AP hormones and expressed additional HRH receptors. Cold stress did not modify the number of ACTH containing cells, but, according to immunostaining, it increased the relative abundance of other AP cell types at the expense of the pool of cells storing no hormones. Cold stress also modified the response to CRH and other HRHs. Most of these phenotypical changes presented a strong sexual dimorphism. These results indicate that pituitary plasticity is even larger than previously thought.