title: Exogenous androstenedione induces formation of follicular cysts and premature luteinization of granulosa cells in the ovary.
abstract: OBJECTIVE
  To investigate the effects of androstenedione on ovarian follicle development.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Female Wistar-Imamichi rats and BDF1 mice.
  
  
  METHODS
  Rats were injected with androstenedione. Ovarian follicles of mice were cultured in the presence of androstenedione.
  
  
  METHODS
  Ovarian morphology; ovarian cell types undergoing apoptosis; ovarian expression of cytochrome P450 aromatase (P450arom), cytochrome P450 side-chain cleavage (P450scc), and cyclin-dependent kinase inhibitor p27(kip1); serum levels of T, E(2), and P in rats; and ultrastructure of granulosa cells from cultured follicles of mice.
  
  
  RESULTS
  In androstenedione-treated rat ovaries, follicular cysts were formed, and apoptotic cells were found in the inner part of granulosa cell layers of antral follicles. Androstenedione administration down-regulated expression of P450arom but up-regulated expression of P450scc and p27(Kip1) in the granulosa cells of antral follicles. Serum T levels were significantly increased in androstenedione-treated rats. In mouse follicles exposed to androstenedione, the granulosa cells contained abundant lipid droplets and mitochondria with complex tubular cristae.
  
  
  CONCLUSIONS
  Excess androgen enhances apoptosis in the inner part of granulosa cell layers of antral follicles, resulting in the formation of follicular cysts. It is also demonstrated that androgen stimulates premature luteinization of granulosa cells.
authors.affiliation: Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Sugao, Miya-mae-ku, Kawasaki 216-8511, Japan. y2okutsu@marianna-u.ac.jp
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okutsu
authors.forename: Masanori T
authors.initials: MT
authors.lastname: Itoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Bunpei
authors.initials: B
authors.lastname: Ishizuka
mesh_terms: D000735:Androstenedione / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005497:Follicular Cyst / Q000139:chemically induced* / Q000473:pathology; D006107:Granulosa Cells / Q000187:drug effects / Q000648:ultrastructure; D034461:Luteinization / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D009865:Oocytes / Q000187:drug effects / Q000648:ultrastructure; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D011085:Polycystic Ovary Syndrome / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C493961:Cdkn1b protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000735:Androstenedione; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase