Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells
Autor: | Roberta Morace, Adriano Angelucci, Antonietta Arcella, Liliya Rostomyan, Felice Giangaspero, Alessandro Colapietro, Luca Ventura, Michela Anna Polidoro, Vincenzo Esposito, Sandra Rotondi, Albert Beckers, Marie Lise Jaffrain-Rea |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Endocrinology Diabetes and Metabolism Clinical Biochemistry nuclear receptors Biochemistry 0302 clinical medicine Endocrinology Fenofibrate Receptor Chemistry Intracellular Signaling Peptides and Proteins General Medicine Middle Aged Diabetes and Metabolism Gene Expression Regulation Neoplastic aryl hydrocarbon receptor interacting protein (AIP) Female Peroxisome proliferator-activated receptor alpha Adult endocrine system medicine.medical_specialty Somatotropic cell WY 14 643 Adolescent Alpha (ethology) 030209 endocrinology & metabolism prolactinomas Prolactin cell 03 medical and health sciences Young Adult Internal medicine medicine Humans PPAR alpha Pituitary Neoplasms Prolactinoma fenofibrate non-functioning pituitary adenomas Aged Cell Proliferation Pyrimidines Somatotrophs Biochemistry (medical) Neoplastic Cell growth 030104 developmental biology Nuclear receptor Gene Expression Regulation Immunostaining |
Zdroj: | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 50(8) |
ISSN: | 1439-4286 |
Popis: | 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. |
Databáze: | OpenAIRE |
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