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Artículo

Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor

Radl, Daniela BetianaIcon ; Ferraris, Maria JimenaIcon ; Boti, Valeria RominaIcon ; Seilicovich, AdrianaIcon ; Sarkar, Dipak Kumar; Pisera, Daniel AlbertoIcon
Fecha de publicación: 03/2011
Editorial: Public Library of Science
Revista: Plos One
ISSN: 1932-6203
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Fisiología

Resumen

Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.
Palabras clave: Dopamine , D2 Receptor Isoform , D2s , Cabergoline , Apoptosis , Lactotropes , Estradiol , P38 Mapk , Anterior Pituitary , Prolactinoma
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/15174
URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018097
DOI: http://dx.doi.org/10.1371/journal.pone.0018097
Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(INBIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Citación
Radl, Daniela Betiana; Ferraris, Maria Jimena; Boti, Valeria Romina; Seilicovich, Adriana; Sarkar, Dipak Kumar; et al.; Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor; Public Library of Science; Plos One; 6; 3; 3-2011; 18097-18104
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