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Published on: February 26, 2019
Role of obestatin on growth hormone secretion: An in vitro approach
Yolanda Pazos1, Carlos J P Alvarez, Jesús P Camiña
1Area de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela, Spain. yolanda.pazos@usc.es
Abstract:
Obestatin, the ghrelin-associated peptide, showed to activate MAPK signaling with no effect on Akt nor cell proliferating activity in rat tumor somatotroph cells (growth cells, GC). A sequential analysis of the obestatin transmembrane signaling pathway indicated a route involving the consecutive activation of G(i), PI3k, novel PKCepsilon, and Src for ERK1/2 activation. Furthermore, obestatin treatment triggers growth hormone (GH) release in the first 30min, being more acute at 15min. At 1h, obestatin treated cells showed the same levels in GH secretion than controls. Added to this functionality, obestatin was secreted by GC cells. Based on the capacity to stimulate GH release from somatotroph cells, obestatin may act directly in the pituitary through an autocrine/paracrine mechanism.
Insights
Obestatin activates MAPK signaling and triggers growth hormone release in rat pituitary cells. This peptide may act locally in the pituitary via autocrine or paracrine signaling.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Signaling
Background:
- Obestatin is a peptide hormone associated with ghrelin.
- Its role in pituitary somatotroph cells (GC) is not fully understood.
- Previous studies have not clarified its signaling pathways or direct effects on growth hormone (GH) secretion.
Purpose of the Study:
- To investigate the signaling pathways activated by obestatin in rat tumor somatotroph cells.
- To determine the effect of obestatin on growth hormone (GH) release.
- To explore the potential autocrine/paracrine role of obestatin in the pituitary.
Main Methods:
- Treatment of rat tumor somatotroph cells with obestatin.
- Analysis of MAPK and Akt signaling pathways.
- Measurement of cell proliferation.
- Assessment of GH secretion over time.
- Investigation of the obestatin transmembrane signaling cascade.
Main Results:
- Obestatin activated MAPK signaling, specifically ERK1/2, but did not affect Akt or cell proliferation.
- A signaling pathway involving G(i), PI3k, PKCepsilon, and Src was identified for ERK1/2 activation.
- Obestatin acutely stimulated GH release within 30 minutes, peaking at 15 minutes.
- GH secretion returned to control levels after 1 hour.
- Obestatin was found to be secreted by the GC cells themselves.
Conclusions:
- Obestatin directly stimulates GH release from somatotroph cells.
- The signaling pathway for obestatin involves sequential activation of G(i), PI3k, PKCepsilon, and Src leading to ERK1/2 activation.
- Obestatin's secretion by GC cells suggests a potential autocrine/paracrine role in pituitary function.
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