Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARα) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH3 cells

Sandra Rotondi; Alessio Modarelli; Maria-Antonietta Oliva; Liliya Rostomyan; Patrizia Sanita; Luca Ventura; Adrian F Daly; Vincenzo Esposito; Adriano Angelucci; Antonietta Arcella; Felice Giangaspero; Albert Beckers; Marie-Lise Jaffrain-Rea

doi:10.1016/j.mce.2016.02.005

Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARα) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH3 cells

Mol Cell Endocrinol. 2016 May 5:426:61-72. doi: 10.1016/j.mce.2016.02.005. Epub 2016 Feb 10.

Affiliations

¹ Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, AQ, Italy; Neuromed Institute, IRCCS, Pozzilli, IS, Italy.
² Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, AQ, Italy.
³ Neuromed Institute, IRCCS, Pozzilli, IS, Italy.
⁴ Endocrinology, CHU of Liège, University of Liège, Belgium.
⁵ Division of Pathology, "San Salvatore" Hospital, L'Aquila, AQ, Italy.
⁶ Neuromed Institute, IRCCS, Pozzilli, IS, Italy; Neurosurgery, Department of Neurology and Psychiatry, University "La Sapienza", Rome, RM, Italy.
⁷ Neuromed Institute, IRCCS, Pozzilli, IS, Italy; Neuropathology, Department of Radiological, Oncological and Anatomopathological Sciences, University "La Sapienza", Rome, RM, Italy.
⁸ Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, AQ, Italy; Neuromed Institute, IRCCS, Pozzilli, IS, Italy. Electronic address: [email protected].

PMID: 26872613
DOI: 10.1016/j.mce.2016.02.005

Abstract

Purpose: To search for a possible role of Peroxisome Proliferator-Activated Receptor α (PPARα), a molecular partner of the Aryl hydrocarbon receptor Interacting Protein (AIP), in somatotropinomas.

Methods: Tumours from 51 acromegalic patients were characterized for PPARα and AIP expression by immunohistochemistry (IHC) and/or Real Time RT-PCR. Data were analysed according to tumour characteristics and pre-operative treatment with somatostatin analogues (SSA). The effects of fenofibrate were studied in GH3 cells in vitro.

Results: PPARα was expressed in most somatotropinomas. A modest relationship was found between PPARα and AIP expression, both being significantly higher in the presence of pre-operative SSA. However, only AIP expression was influenced by the response to treatment. Dual effects of fenofibrate were observed in GH3 cells, consisting of cell growth inhibition and an increase in GH secretion inhibited by octreotide.

Conclusions: PPARα is a new player in somatotropinomas. Potential interactions between PPARα agonists and SSA may deserve further investigation.

Keywords: Acromegaly; Aryl hydrocarbon receptor interacting protein (AIP); Fenofibrate; GH(3) cells; Peroxisome proliferator-activated receptor (PPARα); Somatostatin analogues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoma / metabolism*
Adolescent
Adult
Aged
Animals
Apoptosis
Cell Line
Cell Proliferation
Child
Female
Fenofibrate / pharmacology*
Growth Hormone-Secreting Pituitary Adenoma / metabolism*
Humans
Intracellular Signaling Peptides and Proteins / metabolism*
Male
Middle Aged
PPAR alpha / metabolism*
Pituitary Gland / metabolism
Pituitary Gland / pathology
Rats
Young Adult

Substances

Intracellular Signaling Peptides and Proteins
PPAR alpha
aryl hydrocarbon receptor-interacting protein
Fenofibrate