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Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome.
Reprod Biol Endocrinol. 2020 Dec 07; 18(1):121.RB

Abstract

BACKGROUND

It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS).

METHODS

Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH, n = 30) or without GH treatment (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay.

RESULTS

Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (P < 0.05). The mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly decreased, whereas Bcl-2 was increased in GCs of the PCOS-GH group than those in the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were decreased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were increased in GCs of the PCOS-GH group, compared with those in the PCOS-C group (P < 0.05).

CONCLUSION

OS induced apoptosis and downregulated the PI3K/Akt signaling pathway in patients with PCOS. GH could alleviate apoptosis and activate the PI3K/Akt signaling pathway.

CLINICAL TRIAL REGISTRATION NUMBER

Chinese Clinical Trial Registry. ChiCTR1800019437 . Prospectively registered on October 20, 2018.

Links

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Authors+Show Affiliations

Gong Y
Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, People's Republic of China. Reproductive Medicine Center, Sichuan Provincial Women's and Children's Hospital, The Affiliated Women's and children's Hospital of Chengdu Medical College, Chengdu, Sichuan, People's Republic of China.
Luo S
Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, People's Republic of China.
Fan P
Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, People's Republic of China.
Zhu H
Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, People's Republic of China.
Li Y
Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, People's Republic of China.
Huang W
Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. Weihuang64@163.com. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan, People's Republic of China. Weihuang64@163.com. Department of Reproductive Medicine, West China Second University Hospital of Sichuan University, #1416 Chenglong Road, JinJiang District, Chengdu, Sichuan, 610041, People's Republic of China. Weihuang64@163.com.

MeSH

ApoptosisBlotting, WesternCaspase 3Cells, CulturedFemaleGene Expression RegulationGranulosa CellsGrowth HormoneHumansOocyte RetrievalPhosphatidylinositol 3-KinasesPolycystic Ovary SyndromeProspective StudiesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionSignal Transduction

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

33287836

Citation

Gong, Yan, et al. "Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome." Reproductive Biology and Endocrinology : RB&E, vol. 18, no. 1, 2020, p. 121.
Gong Y, Luo S, Fan P, et al. Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reprod Biol Endocrinol. 2020;18(1):121.
Gong, Y., Luo, S., Fan, P., Zhu, H., Li, Y., & Huang, W. (2020). Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reproductive Biology and Endocrinology : RB&E, 18(1), 121. https://doi.org/10.1186/s12958-020-00677-x
Gong Y, et al. Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome. Reprod Biol Endocrinol. 2020 Dec 7;18(1):121. PubMed PMID: 33287836.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. AU - Gong,Yan, AU - Luo,Shan, AU - Fan,Ping, AU - Zhu,Huili, AU - Li,Yujing, AU - Huang,Wei, Y1 - 2020/12/07/ PY - 2020/09/12/received PY - 2020/11/20/accepted PY - 2020/12/8/entrez PY - 2020/12/9/pubmed PY - 2021/10/5/medline KW - Apoptosis KW - Growth hormone KW - PI3K/Akt signaling KW - Polycystic ovary syndrome KW - Reactive oxygen species SP - 121 EP - 121 JF - Reproductive biology and endocrinology : RB&E JO - Reprod Biol Endocrinol VL - 18 IS - 1 N2 - BACKGROUND: It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS). METHODS: Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH, n = 30) or without GH treatment (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay. RESULTS: Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (P < 0.05). The mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly decreased, whereas Bcl-2 was increased in GCs of the PCOS-GH group than those in the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were decreased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were increased in GCs of the PCOS-GH group, compared with those in the PCOS-C group (P < 0.05). CONCLUSION: OS induced apoptosis and downregulated the PI3K/Akt signaling pathway in patients with PCOS. GH could alleviate apoptosis and activate the PI3K/Akt signaling pathway. CLINICAL TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry. ChiCTR1800019437 . Prospectively registered on October 20, 2018. SN - 1477-7827 UR - https://www.unboundmedicine.com/medline/citation/33287836/Growth_hormone_activates_PI3K/Akt_signaling_and_inhibits_ROS_accumulation_and_apoptosis_in_granulosa_cells_of_patients_with_polycystic_ovary_syndrome_ DB - PRIME DP - Unbound Medicine ER -