Treatment of acromegaly by rosiglitazone via upregulating 15-PGDH in both pituitary adenoma and liver.

Abstract

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver.

• Authors: Yichao Zhang, Meng Wang, Chenxing Ji, Zhengyuan Chen, Hui Yang, Lei Wang, Yifei Yu, Nidan Qiao, Zengyi Ma, Zhao Ye, Xiaoqing Shao, Wenjuan Liu, Yi Wang, Wei Gong, Vladimir Melnikov, Lydia Hu, Eun Jig Lee, Hongying Ye, Yongfei Wang, Yiming Li, Min He, Yao Zhao, Zhaoyun Zhang
• Journal: iScience (iScience) Vol. 24 Issue 9 Pg. 102983 (Sep 24 2021) ISSN: 2589-0042 [Electronic] United States
• PMID: 34485865 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors.