Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol

Po Han Lin; Tsung Hsien Kuo; Chih Chieh Chen; Cai Yun Jian; Chien Wei Chen; Kai Lee Wang; Yuh Chen Kuo; Heng Yi Shen; Shih Min Hsia; Paulus S. Wang; Fu Kong Lieu; Shyi Wu Wang

doi:10.1038/s41598-020-58125-0

Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol

Po Han Lin, Tsung Hsien Kuo, Chih Chieh Chen, Cai Yun Jian, Chien Wei Chen, Kai Lee Wang, Yuh Chen Kuo, Heng Yi Shen, Shih Min Hsia, Paulus S. Wang, Fu Kong Lieu, Shyi Wu Wang

研究成果: 雜誌貢獻 › 文章 › 同行評審

11 引文斯高帕斯（Scopus）

摘要

The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.

原文	英語
文章編號	1576
頁（從 - 到）	1576
期刊	Scientific Reports
卷	10
發行號	1
DOIs	https://doi.org/10.1038/s41598-020-58125-0
出版狀態	已發佈 - 1月 31 2020

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10.1038/s41598-020-58125-0

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Lin, P. H., Kuo, T. H., Chen, C. C., Jian, C. Y., Chen, C. W., Wang, K. L., Kuo, Y. C., Shen, H. Y., Hsia, S. M., Wang, P. S., Lieu, F. K., & Wang, S. W. (2020). Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol. Scientific Reports, 10(1), 1576. 文章 1576. https://doi.org/10.1038/s41598-020-58125-0

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title = "Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol",

abstract = "The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.",

author = "Lin, {Po Han} and Kuo, {Tsung Hsien} and Chen, {Chih Chieh} and Jian, {Cai Yun} and Chen, {Chien Wei} and Wang, {Kai Lee} and Kuo, {Yuh Chen} and Shen, {Heng Yi} and Hsia, {Shih Min} and Wang, {Paulus S.} and Lieu, {Fu Kong} and Wang, {Shyi Wu}",

note = "Funding Information: In this study, the anti-StAR antibody was kindly provided from Dr. D. M. Stocco, Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA. This work was supported by the grants from the Ministry of Science and Technology (MOST 104-2320-B-182-012, MOST 106-2320-B-039-061, and MOST 107-2320-B-182-001), the Taipei City Hospital (2015 No.33), Cheng Hsin General Hospital (CHGH 108-21), and Chang Gung Memorial Hospital Foundation (CMRPD1H0061, CMRPD1H0062, CMRPD1F0291, CMRPD1C0491, and CMRPD1C0492), Taiwan.",

year = "2020",

month = jan,

day = "31",

doi = "10.1038/s41598-020-58125-0",

language = "English",

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T1 - Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol

AU - Lin, Po Han

AU - Kuo, Tsung Hsien

AU - Chen, Chih Chieh

AU - Jian, Cai Yun

AU - Chen, Chien Wei

AU - Wang, Kai Lee

AU - Kuo, Yuh Chen

AU - Shen, Heng Yi

AU - Hsia, Shih Min

AU - Wang, Paulus S.

AU - Lieu, Fu Kong

AU - Wang, Shyi Wu

N1 - Funding Information: In this study, the anti-StAR antibody was kindly provided from Dr. D. M. Stocco, Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA. This work was supported by the grants from the Ministry of Science and Technology (MOST 104-2320-B-182-012, MOST 106-2320-B-039-061, and MOST 107-2320-B-182-001), the Taipei City Hospital (2015 No.33), Cheng Hsin General Hospital (CHGH 108-21), and Chang Gung Memorial Hospital Foundation (CMRPD1H0061, CMRPD1H0062, CMRPD1F0291, CMRPD1C0491, and CMRPD1C0492), Taiwan.

PY - 2020/1/31

Y1 - 2020/1/31

N2 - The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.

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Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol

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