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Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas

Anthony P Heaney1, Manory Fernando, William H Yong

  • 1Department of Medicine, Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California, USA. heaneya@csmc.edu

Nature Medicine
|October 16, 2002
PubMed

Insights

Thiazolidinediones, activating peroxisome proliferator-activated receptor-gamma (PPAR-gamma), show promise for treating Cushing disease. This research found PPAR-gamma in ACTH-secreting pituitary tumors, with its activators inhibiting tumor growth and hormone secretion.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors cause significant morbidity due to excess glucocorticoids.
  • Current treatments, including surgery, have limitations, and effective drug therapies are lacking.

Purpose of the Study:

  • To investigate the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in ACTH-secreting pituitary tumors.
  • To evaluate the therapeutic potential of PPAR-gamma activators for Cushing disease.

Main Methods:

  • Immunohistochemical analysis of PPAR-gamma expression in normal and tumorous pituitary tissues.
  • In vitro studies using human and murine corticotroph tumor cells treated with PPAR-gamma activators.
  • In vivo studies using a murine model of corticotroph tumors treated with rosiglitazone.

Main Results:

  • PPAR-gamma is expressed in normal ACTH-secreting pituitary cells and abundantly in ACTH-secreting pituitary tumors.
  • PPAR-gamma activators induced cell-cycle arrest, apoptosis, and suppressed ACTH secretion in tumor cells.
  • Rosiglitazone treatment prevented tumor development and suppressed hormone secretion in a murine model.

Conclusions:

  • PPAR-gamma is a potential therapeutic target for ACTH-secreting pituitary tumors.
  • Thiazolidinediones, as PPAR-gamma activators, represent a promising therapeutic strategy for Cushing disease.

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