We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Functional PPAR-γ receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas.
- Authors
Heaney, Anthony P.; Fernando, Manory; Yong, William H.; Melmed, Shlomo
- Abstract
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-γ (PPAR-γ) exclusively in normal ACTH-secreting human anterior pituitary cells: PPAR-γ was abundantly expressed in all of six human ACTH-secreting pituitary tumors studied. PPAR-γ activators induced G[sub 0]/G[sub 1] 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.
- Subjects
ADENOMA; PITUITARY cancer; ADRENOCORTICOTROPIC hormone
- Publication
Nature Medicine, 2002, Vol 8, Issue 11, p1281
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm784