title: Effect of androgen onKiss1expression and luteinizing hormone release in female rats.
abstract: Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number ofKiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPVKiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol.Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARCKiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a fewKiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities.
authors.affiliation: Department of Anatomy and NeurobiologyGraduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan kiwata0309@nms.ac.jp.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Anatomy and NeurobiologyGraduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Kunimura
authors.affiliation: Department of Anatomy and NeurobiologyGraduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Anatomy and NeurobiologyGraduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000502:physiology; D007032:Hypothalamus, Anterior / Q000502:physiology; D007150:Immunohistochemistry; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism*; D015287:Neurokinin B / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
chemical_list: C491406:Kiss1 protein, rat; D059648:Kisspeptins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D015287:Neurokinin B; D007986:Luteinizing Hormone
keywords: 5α-dihydrotestosterone; androgen receptor; hyperandrogenism/hyperandrogenemia; kisspeptin