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Horm Metab Res 2018; 50(08): 640-647
DOI: 10.1055/a-0633-2706
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Michela Anna Polidoro   *
1   Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
,
Sandra Rotondi
1   Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
,
Roberta Morace
2   Neuromed Institute, IRCCS, Pozzilli, Italy
,
Liliya Rostomyan
3   Endocrinology, CHU of Liège, University of Liège, Liège, Belgium
,
Alessandro Colapietro
1   Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
,
Antonietta Arcella
2   Neuromed Institute, IRCCS, Pozzilli, Italy
,
Luca Ventura
4   Division of Pathology, “San Salvatore” Hospital, L’Aquila, Italy
,
Adriano Angelucci
1   Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
,
Felice Giangaspero
2   Neuromed Institute, IRCCS, Pozzilli, Italy
5   Department of Radiological, Oncological and Anatomopathological Sciences, University “La Sapienza”, Rome, Italy
,
Vincenzo Esposito
2   Neuromed Institute, IRCCS, Pozzilli, Italy
6   Department of Neurology and Psychiatry, University “La Sapienza”, Rome, Italy
,
Albert Beckers
3   Endocrinology, CHU of Liège, University of Liège, Liège, Belgium
,
Marie-Lise Jaffrain-Rea
1   Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
2   Neuromed Institute, IRCCS, Pozzilli, Italy
› Author Affiliations
Further Information

Publication History

received 13 February 2018

accepted 15 May 2018

Publication Date:
18 July 2018 (online)

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Abstract

Peroxisome 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.

Key words

non-functioning pituitary adenomas - prolactinomas - nuclear receptors - aryl hydrocarbon receptor interacting protein (AIP) - fenofibrate - WY 14 643

* Michela Anna Polidoro is currently a fellow in Immunology, Humanitas Research Hospital, 20089, Rozzano, Italy


Supplementary Material

 

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