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, Sandra Rotondi, Roberta Morace, Liliya Rostomyan, Alessandro Colapietro, Antonietta Arcella, Luca Ventura, Adriano Angelucci, Felice Giangaspero, Vincenzo Esposito, Albert Beckers, Marie Lise Jaffrain-Rea

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)640-647
Number of pages8
JournalHormone and Metabolic Research
Volume50
Issue number8
DOIs
Publication statusPublished - Jul 18 2018

Fingerprint

PPAR alpha
Pituitary Neoplasms
Tumors
Lactotrophs
Somatotrophs
Fenofibrate
Gonadotrophs
Prolactinoma
Cell growth
Tumor Burden
Pharmaceutical Preparations
Real-Time Polymerase Chain Reaction
Neoplasms
Cell Count
Immunohistochemistry
Cells
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells. / Polidoro, Michela Anna; Rotondi, Sandra; Morace, Roberta; Rostomyan, Liliya; Colapietro, Alessandro; Arcella, Antonietta; Ventura, Luca; Angelucci, Adriano; Giangaspero, Felice; Esposito, Vincenzo; Beckers, Albert; Jaffrain-Rea, Marie Lise.

In: Hormone and Metabolic Research, Vol. 50, No. 8, 18.07.2018, p. 640-647.

Research output: Contribution to journalArticle

Polidoro, Michela Anna ; Rotondi, Sandra ; Morace, Roberta ; Rostomyan, Liliya ; Colapietro, Alessandro ; Arcella, Antonietta ; Ventura, Luca ; Angelucci, Adriano ; Giangaspero, Felice ; Esposito, Vincenzo ; Beckers, Albert ; Jaffrain-Rea, Marie Lise. / Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells. In: Hormone and Metabolic Research. 2018 ; Vol. 50, No. 8. pp. 640-647.
@article{6ce4376d868d4d17a4852e03e35ddc1b,
title = "Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells",
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.",
keywords = "aryl hydrocarbon receptor interacting protein (AIP), fenofibrate, non-functioning pituitary adenomas, nuclear receptors, prolactinomas, WY 14 643",
author = "Polidoro, {Michela Anna} and Sandra Rotondi and Roberta Morace and Liliya Rostomyan and Alessandro Colapietro and Antonietta Arcella and Luca Ventura and Adriano Angelucci and Felice Giangaspero and Vincenzo Esposito and Albert Beckers and Jaffrain-Rea, {Marie Lise}",
year = "2018",
month = "7",
day = "18",
doi = "10.1055/a-0633-2706",
language = "English",
volume = "50",
pages = "640--647",
journal = "Hormone and Metabolic Research",
issn = "0018-5043",
publisher = "Georg Thieme Verlag",
number = "8",

}

TY - JOUR

T1 - Expression of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Non-Somatotroph Pituitary Tumours and the Effects of PPARα Agonists on MMQ Cells

AU - Polidoro, Michela Anna

AU - Rotondi, Sandra

AU - Morace, Roberta

AU - Rostomyan, Liliya

AU - Colapietro, Alessandro

AU - Arcella, Antonietta

AU - Ventura, Luca

AU - Angelucci, Adriano

AU - Giangaspero, Felice

AU - Esposito, Vincenzo

AU - Beckers, Albert

AU - Jaffrain-Rea, Marie Lise

PY - 2018/7/18

Y1 - 2018/7/18

N2 - 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.

AB - 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.

KW - aryl hydrocarbon receptor interacting protein (AIP)

KW - fenofibrate

KW - non-functioning pituitary adenomas

KW - nuclear receptors

KW - prolactinomas

KW - WY 14 643

UR - http://www.scopus.com/inward/record.url?scp=85050261317&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050261317&partnerID=8YFLogxK

U2 - 10.1055/a-0633-2706

DO - 10.1055/a-0633-2706

M3 - Article

C2 - 30021235

AN - SCOPUS:85050261317

VL - 50

SP - 640

EP - 647

JO - Hormone and Metabolic Research

JF - Hormone and Metabolic Research

SN - 0018-5043

IS - 8

ER -