title: Prior attenuation of KiSS1/GPR54 signaling in the anteroventral periventricular nucleus is a trigger for the delayed effect induced by neonatal exposure to 17alpha-ethynylestradiol in female rats.
abstract: Neonatal exposure to 17alpha-ethynylestradiol (EE) causes delayed effect, a late-occurring irreversible damage to reproductive functions characterized by the early onset of age-matched abnormal estrous cycling. To clarify the involvement of a hypothalamic key cycling regulator KiSS1/GPR54 in the delayed effect, we investigated artificially induced LH surges and KiSS1 mRNA expression in the anteroventral periventricular nucleus (AVPV) of cycling young adult rats neonatally exposed to EE, and compared these parameters to those in about 5 months old middle-aged rats. KiSS1 mRNA expression, the number of KiSS1-positive cells and KiSS1/ERα co-expressing cells in the AVPV decreased in both EE-exposed and middle-aged rats. The peak area and levels of LH surge dose-dependently decreased in EE-exposed rats, and reduction was more evident in middle-aged rats. These results indicate that the prior attenuation of KiSS1 and consequent depression of LH surges plays a key role in the onset of abnormal estrous cycling in the delayed effect.
authors.affiliation: Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan; Development Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ichimura
authors.affiliation: Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.affiliation: Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Usuda
authors.affiliation: Behavioral Neuroscience Laboratory, Graduate School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yokosuka
authors.affiliation: Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.affiliation: Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: midoriy@nihs.go.jp.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007032:Hypothalamus, Anterior / Q000187:drug effects* / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics*; D007986:Luteinizing Hormone / Q000097:blood*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000074502:Receptors, Kisspeptin-1; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C491406:Kiss1 protein, rat; C492247:Kiss1r protein, rat; D059648:Kisspeptins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D004997:Ethinyl Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: 17Alpha-ethynylestradiol; AVPV; Delayed effect; EDCs; GPR54; Kisspeptin; LH surge; Neonatal exposure