title: The role of estrogen receptor subtypes for induction of delayed effects on the estrous cycle and female reproductive organs in rats.
abstract: It has been reported that neonatal exposure to estrogens at relatively low doses can induce early onset anovulation as a delayed effect in female rats. Dysfunction of kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) was proposed to be a trigger for this effect. To determine the roles of estrogen receptor (ER) subtypes in the induction of delayed effects, we conducted a series of experiments using Donryu rats to examine whether neonatal injection of an ERα agonist (PPT), an ERβ agonist (DPN) or an ERα antagonist (ICI) could induce delayed effects. Also, involvement of the kisspeptin neurons in the AVPV for induction of delayed effect by PPT and DPN was investigated. We observed that neonatal exposure to PPT, DPN and ICI induced the early onset of abnormal estrous cyclicity after sexual maturation, suggesting that the compounds capable of inducing delayed effects are not limited to ERα agonists. On the other hand, the data suggested the possibility that DPN and ICI functioned partially as ERα agonists in the neonatal brain. Regardless of the agents used, there is a possibility that dysfunction of kisspeptin neurons in the AVPV might contribute to induction of early onset anovulation.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ichimura
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 12 Fuchu-shi, Tokyo 183-8509, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kuwata
authors.affiliation: Laboratory of Veterinary Physiology, 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: Food Safety Commission, Akasaka Park Bld. 22nd F. Akasaka 5-2-20, Minato-ku, Tokyo 107-6122, Japan. Electronic address: midori.yoshida@cao.go.jp.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000858:Anovulation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D065171:Estrogen Receptor Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D007032:Hypothalamus, Anterior / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059648:Kisspeptins / Q000378:metabolism; D008599:Menstruation Disturbances / Q000139:chemically induced* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D014018:Tissue Distribution; D066007:Toxicokinetics; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; C491406:Kiss1 protein, rat; D059648:Kisspeptins
keywords: Delayed effect; ER alpha; ER beta; Estrous cycle; Kisspeptin