title: The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression.
abstract: Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARγ and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARγ dependent PTEN/p-Akt expression in the granulosa cells.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Jou
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shee-Uan
authors.initials: SU
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Shih
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hong-Nerng
authors.initials: HN
authors.lastname: Ho
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000728:Androgens; D047495:PPAR gamma; D013196:Dihydrotestosterone; D005640:Follicle Stimulating Hormone; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase