Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells

Author:

Polidoro Michela1,Rotondi Sandra1,Morace Roberta2,Rostomyan Liliya3,Colapietro Alessandro1,Arcella Antonietta2,Ventura Luca4,Angelucci Adriano1,Giangaspero Felice25,Esposito Vincenzo26,Beckers Albert3,Jaffrain-Rea Marie-Lise12

Affiliation:

1. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

2. Neuromed Institute, IRCCS, Pozzilli, Italy

3. Endocrinology, CHU of Liège, University of Liège, Liège, Belgium

4. Division of Pathology, “San Salvatore” Hospital, L’Aquila, Italy

5. Department of Radiological, Oncological and Anatomopathological Sciences, University “La Sapienza”, Rome, Italy

6. Department of Neurology and Psychiatry, University “La Sapienza”, Rome, Italy

Abstract

AbstractPeroxisome proliferator-activated receptor alpha (PPARα) has been involved in the regulation of somatotroph tumour cells and may be targeted by different drugs, some of them are in current clinical use. The aim of this study was to investigate the expression of PPARα in additional phenotypes of pituitary adenomas (PA), the relationship between PPARα and its potential molecular partner aryl hydrocarbon receptor interacting protein (AIP) in these tumours, and the effects of PPARα agonists on lactotroph cells. Seventy-five human PA – 57 non-functioning (NFPA) and 18 prolactinomas (PRL-PA) – were characterised for PPARα and AIP expression by real time RT-PCR and/or immunohistochemistry (IHC), and the effects of fenofibrate and WY 14 643 on MMQ cells were studied in vitro. PPARα was expressed in a majority of PA. PPARα immunostaining was observed in 93.7% PRL-PA vs. 60.6% NFPA (p=0.016), the opposite being found for AIP (83.3% in NFPA vs. 43.7% in PRL-PA, p=0.003). PPARα expression was unrelated to gonadotroph differentiation in NFPA, but positively correlated with tumour volume in PRL-PA. Both drugs significantly reduced MMQ cell growth at high concentrations (100–200 μM). At the same time, despite modest stimulating effects on PRL secretion were observed, these were overcome by the reduction in cell number. In conclusion, PPARα is commonly expressed by PRL-PA and NFPA, regardless of AIP, and may represent a new target of PPARα agonists.

Publisher

Georg Thieme Verlag KG

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,General Medicine,Endocrinology, Diabetes and Metabolism

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