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
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