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

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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.

Original language	English
Article number	1576
Pages (from-to)	1576
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-58125-0
Publication status	Published - Jan 31 2020

ASJC Scopus subject areas

General

Access to Document

10.1038/s41598-020-58125-0

Cite this

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. Article 1576. https://doi.org/10.1038/s41598-020-58125-0

@article{d41d7fcee15946d19bd7b0fe09241d64,

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 = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = jan,

day = "31",

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

language = "English",

volume = "10",

pages = "1576",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

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

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85078832525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85078832525&partnerID=8YFLogxK

U2 - 10.1038/s41598-020-58125-0

DO - 10.1038/s41598-020-58125-0

M3 - Article

C2 - 32005928

AN - SCOPUS:85078832525

SN - 2045-2322

VL - 10

SP - 1576

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 1576

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this