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27.10.2017 | Original Article

PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line

verfasst von: Carmelina Di Pasquale, Erica Gentilin, Simona Falletta, Mariaenrica Bellio, Mattia Buratto, Ettore degli Uberti, Maria Chiara Zatelli

Erschienen in: Endocrine | Ausgabe 2/2018

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Abstract

Purpose

Insulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion.

Methods

Cell viability, GH secretion, Akt, and Erk 1/2 phosphorylation levels in the rat GH3 cell line were assessed under treatment with IGF1 and/or everolimus, an mTOR inhitior.

Results

We found that IGF1 improves rat GH3 somatotroph cell viability via the PI3K/Akt/mTOR pathway and confirmed that IGF1 exerts a negative feedback on GH secretion by a transcriptional mechanism. We demonstrated that the negative IGF1 loop on GH secretion requires Akt activation that seems to play a pivotal role in the control of GH secretion. Furthermore, Akt activation is independent of PI3K and probably mediated by mTORC2. In addition, we found that Erk 1/2 is not involved in GH3 cell viability regulation, but may have a role in controlling GH secretion, independently of IGF1.

Conclusion

Our data confirm that mTOR inhibitors may be useful to reduce pituitary adenoma cell viability, while Erk 1/2 pathway may be considered as a useful therapeutic target to control GH secretion. Our results open the field for further studies searching for effective drugs to control GH hyper-secretion.

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Titel: PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line
verfasst von: Carmelina Di Pasquale
Erica Gentilin
Simona Falletta
Mariaenrica Bellio
Mattia Buratto
Ettore degli Uberti
Maria Chiara Zatelli
Publikationsdatum: 27.10.2017
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-017-1432-0

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