title: Pubertal timing after neonatal diethylstilbestrol exposure in female rats: neuroendocrine vs peripheral effects and additive role of prenatal food restriction.
abstract: We studied the effects of neonatal exposure to diethylstilbestrol (DES) on pubertal timing in female rats. We examined associated neuroendocrine changes and effects of prenatal food restriction. Age at vaginal opening was advanced after exposure to 10 μg/kg/d of DES and delayed after 1 μg/kg/d (subcutaneous injections). Using this lower dose, pulsatile GnRH secretion was slower at 25 days of age. Both doses reduced KiSS1 mRNA levels at 15 days of age. Using functional Kisspeptin promoter assay, 1 or 10 μM DES reduced or increased KISS1 transcription, respectively. Leptin stimulatory effect on GnRH secretion in vitro (15 days of age) was reduced after prenatal food restriction and neonatal DES exposure (higher dose), both effects being cumulative. Thus, alterations in pubertal timing by DES neonatally are not unequivocally toward precocity, the level of exposure being critical. We provide evidence of neuroendocrine disruption and interaction with prenatal food availability.
authors: Development Neuroendocrinology Unit, GIGA Neurosciences, University of Liege, CHU Sart-Timan, B4000 Liege, Belgium.
authors: Delphine
authors: D
authors: Franssen
authors: Development Neuroendocrinology Unit, GIGA Neurosciences, University of Liege, CHU Sart-Timan, B4000 Liege, Belgium.
authors: Yiannis S
authors: YS
authors: Ioannou
authors: Development Neuroendocrinology Unit, GIGA Neurosciences, University of Liege, CHU Sart-Timan, B4000 Liege, Belgium.
authors: Alexandra
authors: A
authors: Alvarez-real
authors: Development Neuroendocrinology Unit, GIGA Neurosciences, University of Liege, CHU Sart-Timan, B4000 Liege, Belgium.
authors: Arlette
authors: A
authors: Gerard
authors: Pediatric Endocrinology, University of Hanover, Germany.
authors: Johanna K
authors: JK
authors: Mueller
authors: Pediatric Endocrinology, University of Hanover, Germany.
authors: Sabine
authors: S
authors: Heger
authors: Development Neuroendocrinology Unit, GIGA Neurosciences, University of Liege, CHU Sart-Timan, B4000 Liege, Belgium.
authors: Jean-Pierre
authors: JP
authors: Bourguignon
authors: Development Neuroendocrinology Unit, GIGA Neurosciences, University of Liege, CHU Sart-Timan, B4000 Liege, Belgium. Electronic address: asparent@ulg.ac.be.
authors: Anne-Simone
authors: AS
authors: Parent
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004054:Diethylstilbestrol / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005508:Food Deprivation; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics*; D020738:Leptin / Q000097:blood; D051379:Mice; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects*; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
chemical_list: D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D020738:Leptin; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol
keywords: Diethylstilbestrol; Hypothalamus; Kisspeptin; Leptin; Puberty