High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.
The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China.|Center for Reproductive Medicine, Tai'an Central Hospital, Tai'an, 271000, China.
Tao
T
Liu
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|Center for Reproductive Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yu-Qian
YQ
Cui
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China.
Han
H
Zhao
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China.
Hong-Bin
HB
Liu
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China.
Shi-Dou
SD
Zhao
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China.
Yuan
Y
Gao
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China.
Xiao-Li
XL
Mu
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. gaof@ioz.ac.cn.
Fei
F
Gao
Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China. chenzijiang@hotmail.com.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China. chenzijiang@hotmail.com.|The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China. chenzijiang@hotmail.com.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, 250021, China. chenzijiang@hotmail.com.
Zi-Jiang
ZJ
Chen
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D011967:Receptors, Gonadotropin / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000728:Androgens; D012333:RNA, Messenger; D011962:Receptors, FSH; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; D013739:Testosterone; D005640:Follicle Stimulating Hormone
follicle; follicle-stimulating hormone; polycystic ovary syndrome; testosterone