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

iScience

卷:24

Eun Jig Lee¹  Zhaoyun Zhang²  Lydia Hu³  Lei Wang⁴  Xiaoqing Shao⁵  Yifei Yu⁵  Wei Gong⁵  Yao Zhao⁵  Yongfei Wang⁵  Yi Wang⁵  Min He⁵  Meng Wang⁵  Wenjuan Liu⁵  Hongying Ye⁶  Hui Yang⁷  Yiming Li⁸  Chenxing Ji⁸  Zhengyuan Chen⁸  Yichao Zhang⁸  Nidan Qiao⁸  Zengyi Ma⁸  Zhao Ye⁸  Vladimir Melnikov⁹ 

[1] Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37966, USA;

[2] Shanghai Pituitary Tumor Center, Shanghai 200040, China;

[3] Department of Biochemistry &

[4] Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, Shanghai 200032, China;

[5] Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China;

[6] Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea;

[7] Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510000, China;

[8] Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China;

[9] Shanghai Medical College, Fudan University, Shanghai 200040, China;

关键词: Medicine;    Human specimen;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown