Resistin regulates pituitary somatotrope cell function through the activation of multiple signaling pathways.

Abstract:

:The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues and organs, including the pituitary. However, there is no information on whether resistin, as described previously for other adipokines such as leptin and adiponectin, could regulate this gland. Likewise, the molecular basis of resistin actions remains largely unexplored. Here we show that administration of resistin to dispersed rat anterior pituitary cells increased GH release in both the short (4 h) and long (24 h) term, decreased mRNA levels of the receptor of the somatotrope regulator ghrelin, and increased free cytosolic Ca(2+) concentration in single somatotropes. By means of a pharmacological approach, we found that the stimulatory action of resistin occurs through a Gs protein-dependent mechanism and that the adenylate cyclase/cAMP/protein kinase A pathway, the phosphatidylinositol 3-kinase/Akt pathway, protein kinase C, and extracellular Ca(2+) entry through L-type voltage-sensitive Ca(2+) channels are essential players in mediating the effects of resistin on somatotropes. Taken together, our results demonstrate for the first time a regulatory role for resistin on somatotrope function and provide novel insights on the intracellular mechanisms activated by this protein.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Rodríguez-Pacheco F,Vázquez-Martínez R,Martínez-Fuentes AJ,Pulido MR,Gahete MD,Vaudry H,Gracia-Navarro F,Diéguez C,Castaño JP,Malagón MM

doi

10.1210/en.2009-0116

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

4643-52

issue

10

eissn

0013-7227

issn

1945-7170

pii

en.2009-0116

journal_volume

150

pub_type

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