Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis.
Increasing evidence has shown that excess androgen may be a main cause of polycystic ovary syndrome (PCOS). However, the molecular mechanism of androgen action on the ovary is unclear. To investigate the possible impacts of androgen on early follicular development, neonatal mouse ovaries mainly containing primordial follicles were cultured with testosterone. We demonstrated that the number of primary follicles was increased after 10 d culture with testosterone treatment via phosphatidylinositol 3-kinase/Akt pathway. Androgen induced Forkhead box (Foxo)-3a activation, and translocation of Foxo3a protein from oocyte nuclei to cytoplasm, which might be a key step for primordial follicle activation. Interestingly, testosterone was also capable of down-regulating growth and differentiation factor-9 expression via its receptor. In summary, we infer that intraovarian excess androgen in PCOS might result in excess early follicles by inducing oocyte Foxo3a translocation and follicular arrest by down-regulating growth and differentiation factor-9 expression.
Yang
Jun-Ling
JL
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Zhang
Chun-Ping
CP
Li
Lei
L
Huang
Lin
L
Ji
Shao-Yang
SY
Lu
Cui-Ling
CL
Fan
Cui-Hong
CH
Cai
Huan
H
Ren
Yu
Y
Hu
Zhao-Yuan
ZY
Gao
Fei
F
Liu
Yi-Xun
YX
D000728:Androgens / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D055429:Growth Differentiation Factor 9 / Q000235:genetics*; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D010766:Phosphorylation; D010957:Plasmids; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013737:Testis / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology
D000728:Androgens; D017931:DNA Primers; C496506:Foxa3 protein, mouse; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D012333:RNA, Messenger; D051543:Hepatocyte Nuclear Factor 3-gamma; D013739:Testosterone; D051057:Proto-Oncogene Proteins c-akt