iScience (Sep 2021)
Treatment of acromegaly by rosiglitazone via upregulating 15-PGDH in both pituitary adenoma and liver
- 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
Affiliations
- Yichao Zhang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Meng Wang
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Chenxing Ji
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Zhengyuan Chen
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Hui Yang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510000, China
- Lei Wang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, Shanghai 200032, China
- Yifei Yu
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Nidan Qiao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Zengyi Ma
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Zhao Ye
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Xiaoqing Shao
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Wenjuan Liu
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Yi Wang
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Wei Gong
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Vladimir Melnikov
- Shanghai Medical College, Fudan University, Shanghai 200040, China
- Lydia Hu
- Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37966, USA
- Eun Jig Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Hongying Ye
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Yongfei Wang
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Yiming Li
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- Min He
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; Shanghai Pituitary Tumor Center, Shanghai 200040, China; Corresponding author
- Yao Zhao
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; Shanghai Pituitary Tumor Center, Shanghai 200040, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai 200040, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200040, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai 200040, China; Corresponding author
- Zhaoyun Zhang
- Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; Shanghai Pituitary Tumor Center, Shanghai 200040, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 9
p. 102983
Abstract
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.
