title: The advancement of the onset of vaginal opening in female rats subjected to chronic testosterone treatment occurs independently of hypothalamic Kiss1 and RFRP expression.
abstract: OBJECTIVE
  The neonatal and/or prepubertal androgen milieu affects sexual maturation. In rodents, neonatal chronic testosterone treatment, which is used as a model of polycystic ovary syndrome (PCOS), results in the onset of vaginal opening occurring earlier in the pubertal period.
  
  
  METHODS
  In the present study, the changes in hypothalamic Kiss1 (a gonadotropin-releasing hormone (GnRH)-stimulating factor) and RF-amide related peptide (RFRP; a GnRH inhibitory factor) mRNA expression induced by testosterone treatment were examined in order to clarify whether these factors are involved in the testosterone-induced acceleration of sexual maturation.
  
  
  RESULTS
  The onset of vaginal opening occurred earlier and uterine weight was increased in female rats subjected to chronic (from postnatal day 23 to day 31) testosterone treatment. Contrary to our expectations, the rats' hypothalamic Kiss1 and Kiss1 receptor mRNA levels were not changed, and their serum luteinizing hormone (LH) levels were decreased. Although hypothalamic RFRP mRNA expression was decreased in the testosterone-treated rats, this change was not reflected in their serum LH levels.
  
  
  CONCLUSIONS
  These results indicate that the advancement of sexual maturation observed in chronic testosterone-treated rats might be caused by a peripheral, rather than a central, mechanism.
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-Cho, Tokushima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-Cho, Tokushima, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-Cho, Tokushima, Japan.
authors.forename: Altankhuu
authors.initials: A
authors.lastname: Tungalagsuvd
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-Cho, Tokushima, Japan.
authors.forename: Munkhsaikhan
authors.initials: M
authors.lastname: Munkhzaya
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-Cho, Tokushima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Department of Reproductive and Menopausal Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-Cho, Tokushima, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Irahara
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D059648:Kisspeptins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects*
chemical_list: D000728:Androgens; C491406:Kiss1 protein, rat; C492247:Kiss1r protein, rat; D059648:Kisspeptins; D009479:Neuropeptides; C416987:RFamide peptide; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone