Nature Medicine8, 1281 - 1287 (2002)
Published online: 15 October 2002; | doi:10.1038/nm784
Functional PPAR- receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas
Anthony P. Heaney1, Manory Fernando1, William H. Yong2
& Shlomo Melmed1
1
Department of Medicine, Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California, USA
2
Department of Pathology, Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California, USA
Correspondence should be addressed to Anthony P. Heaney heaneya@csmc.edu
Adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors are associated with high morbidity due to excess glucocorticoid production. No suitable drug therapies are currently available, and surgical excision is not invariably curative. Here we demonstrate immunoreactive expression of the nuclear hormone receptor peroxisome proliferator-activated receptor- (PPAR-) exclusively in normal ACTH-secreting human anterior pituitary cells: PPAR- was abundantly expressed in all of six human ACTH-secreting pituitary tumors studied. PPAR- activators induced G0/G1 cell-cycle arrest and apoptosis and suppressed ACTH secretion in human and murine corticotroph tumor cells. Development of murine corticotroph tumors, generated by subcutaneous injection of ACTH-secreting AtT20 cells, was prevented in four of five mice treated with the thiazolidinedione compound rosiglitazone, and ACTH and corticosterone secretion was suppressed in all treated mice. Based on these findings, thiazolidinediones may be an effective therapy for Cushing disease
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