Reach further, in an Open Access Journal Endocrinology, Diabetes & Metabolism Case Reports

ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2006) 11 OC5 

The overexpression Pit-1 pathway, switch on by RET, get into apoptosis fate

CM Cañibano Acebes, A Vidal, MG Borrello, C Diéguez & CV Alcarez

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RET is a tyrosine-kinase receptor having a GPI-linked co-receptor or GFRα. Moreover, RET has four different ligands (GDNF, NTN, ART and PSP) with its respective co-receptor (GFRα-1,-2,-3 and 4). Pituitary cells are differentiated specialized secretory cells. Sommatotrophs are responsible for growth during infancy and puberty until achievement of the final adult height. Although genetic factors leading to somatotroph hypoplasia are well known, no much is known about the mechanisms controlling somatotroph cell proliferation.

Recently, we have demonstrated the expression of Ret, GDNF and GFRα1 from all pituitary secretory cells exclusively on the sommatotrophs in both rats and humans (Urbano et al., 2001; Japón et al., 2002). In this work we intend to characterize the role of RET in somatotrophs. Thus we used primary monolayer cultures of rat AP cells as well as the GH4C1 cell line. Transfecting the RET receptor allow us to uncover a pathway where Ret is regulating sommatotroph cell function through potently inducing Pit-1 expression, as assessed in terms of both mRNA and protein levels. More importantly, Ret-induced Pit-1 overexpression, led to a Pit-1-dependent p53 increase and apoptosis, both of which were prevented by co-transfecting Pit-1 siRNA. We also found that the pathway mediating these effects of Ret involved activation of PKCd, JNK, c/EBPα and CREB. Finally, by transfecting different isoforms and mutated-forms of the RET receptor we found that RET-induced apoptosis in somatotroph cell is unrelated to the kinase activity of the receptor.

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