BACKGROUND: An increase in development of excitatory inputs along with a decline in inhibitory inputs ultimately govern the timely increased secretion of hypothalamic luteinizing hormone-releasing hormone (LHRH) at the time of puberty. As chronic alcohol (ALC) exposure acts at the hypothalamic level to suppress LHRH secretion and delay puberty, we assessed its ability to differentially affect the expression of key puberty-related proteins. METHODS: ALC was administered to female rats from days 27 to 33, at which time animals were killed and tissues collected for protein expression. In the medial basal hypothalamus (MBH), we assessed kisspeptin (Kp) 10, an excitatory peptide critical for prepubertal LHRH secretion, and Lin28b, a peptide with an inhibitory influence on puberty. As a direct mechanism of action of Lin28b was not known, we determined whether its central administration could induce dynorphin (DYN), a peptide that is inhibitory on LHRH secretion. Also, ALC's effect on DYN protein expression was assessed, as well as its effect on DYN release in vitro. RESULTS: ALC markedly suppressed (p < 0.01) the expression of the excitatory Kp protein, while at the same time increased (p < 0.001) the expression of inhibitory Lin28b protein. Subsequently, we showed for the first time that the central administration of Lin28b stimulated (p < 0.01) the synthesis of DYN. Finally, ALC also induced (p < 0.01) the protein expression and stimulated (p < 0.01) the in vitro release of DYN from the MBH. CONCLUSIONS: These results indicate that ALC can simultaneously and differentially alter both excitatory and inhibitory influences governing pubertal development, show for the first time a mechanism of action by which Lin28b exerts its prepubertal inhibitory tone, and further demonstrate the negative influences of ALC on the pubertal process.
BACKGROUND: An increase in development of excitatory inputs along with a decline in inhibitory inputs ultimately govern the timely increased secretion of hypothalamic luteinizing hormone-releasing hormone (LHRH) at the time of puberty. As chronic alcohol (ALC) exposure acts at the hypothalamic level to suppress LHRH secretion and delay puberty, we assessed its ability to differentially affect the expression of key puberty-related proteins. METHODS:ALC was administered to female rats from days 27 to 33, at which time animals were killed and tissues collected for protein expression. In the medial basal hypothalamus (MBH), we assessed kisspeptin (Kp) 10, an excitatory peptide critical for prepubertal LHRH secretion, and Lin28b, a peptide with an inhibitory influence on puberty. As a direct mechanism of action of Lin28b was not known, we determined whether its central administration could induce dynorphin (DYN), a peptide that is inhibitory on LHRH secretion. Also, ALC's effect on DYN protein expression was assessed, as well as its effect on DYN release in vitro. RESULTS:ALC markedly suppressed (p < 0.01) the expression of the excitatory Kp protein, while at the same time increased (p < 0.001) the expression of inhibitory Lin28b protein. Subsequently, we showed for the first time that the central administration of Lin28b stimulated (p < 0.01) the synthesis of DYN. Finally, ALC also induced (p < 0.01) the protein expression and stimulated (p < 0.01) the in vitro release of DYN from the MBH. CONCLUSIONS: These results indicate that ALC can simultaneously and differentially alter both excitatory and inhibitory influences governing pubertal development, show for the first time a mechanism of action by which Lin28b exerts its prepubertal inhibitory tone, and further demonstrate the negative influences of ALC on the pubertal process.
Authors: Patrick Sulem; Daniel F Gudbjartsson; Thorunn Rafnar; Hilma Holm; Elinborg J Olafsdottir; Gudridur H Olafsdottir; Thorvaldur Jonsson; Peter Alexandersen; Bjarke Feenstra; Heather A Boyd; Katja K Aben; Andre L M Verbeek; Nel Roeleveld; Aslaug Jonasdottir; Unnur Styrkarsdottir; Valgerdur Steinthorsdottir; Ari Karason; Simon N Stacey; Julius Gudmundsson; Margret Jakobsdottir; Gudmar Thorleifsson; Gudmundur Hardarson; Jeffrey Gulcher; Augustine Kong; Lambertus A Kiemeney; Mads Melbye; Claus Christiansen; Laufey Tryggvadottir; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2009-05-17 Impact factor: 38.330
Authors: S Sangiao-Alvarellos; M Manfredi-Lozano; F Ruiz-Pino; V M Navarro; M A Sánchez-Garrido; S Leon; C Dieguez; F Cordido; V Matagne; G A Dissen; S R Ojeda; L Pinilla; M Tena-Sempere Journal: Endocrinology Date: 2013-01-04 Impact factor: 4.736
Authors: Robert L Goodman; Stanley M Hileman; Casey C Nestor; Katrina L Porter; John M Connors; Steve L Hardy; Robert P Millar; Maria Cernea; Lique M Coolen; Michael N Lehman Journal: Endocrinology Date: 2013-08-19 Impact factor: 4.736
Authors: Jennifer D Peck; B Mitchell Peck; Valerie J Skaggs; Miyuki Fukushima; Howard B Kaplan Journal: J Adolesc Health Date: 2010-09-16 Impact factor: 5.012
Authors: John R B Perry; Lisette Stolk; Nora Franceschini; Kathryn L Lunetta; Guangju Zhai; Patrick F McArdle; Albert V Smith; Thor Aspelund; Stefania Bandinelli; Eric Boerwinkle; Lynn Cherkas; Gudny Eiriksdottir; Karol Estrada; Luigi Ferrucci; Aaron R Folsom; Melissa Garcia; Vilmundur Gudnason; Albert Hofman; David Karasik; Douglas P Kiel; Lenore J Launer; Joyce van Meurs; Michael A Nalls; Fernando Rivadeneira; Alan R Shuldiner; Andrew Singleton; Nicole Soranzo; Toshiko Tanaka; Jenny A Visser; Michael N Weedon; Scott G Wilson; Vivian Zhuang; Elizabeth A Streeten; Tamara B Harris; Anna Murray; Tim D Spector; Ellen W Demerath; André G Uitterlinden; Joanne M Murabito Journal: Nat Genet Date: 2009-05-17 Impact factor: 38.330
Authors: Cathy E Elks; John R B Perry; Patrick Sulem; Daniel I Chasman; Nora Franceschini; Chunyan He; Kathryn L Lunetta; Jenny A Visser; Enda M Byrne; Diana L Cousminer; Daniel F Gudbjartsson; Tõnu Esko; Bjarke Feenstra; Jouke-Jan Hottenga; Daniel L Koller; Zoltán Kutalik; Peng Lin; Massimo Mangino; Mara Marongiu; Patrick F McArdle; Albert V Smith; Lisette Stolk; Sophie H van Wingerden; Jing Hua Zhao; Eva Albrecht; Tanguy Corre; Erik Ingelsson; Caroline Hayward; Patrik K E Magnusson; Erin N Smith; Shelia Ulivi; Nicole M Warrington; Lina Zgaga; Helen Alavere; Najaf Amin; Thor Aspelund; Stefania Bandinelli; Inês Barroso; Gerald S Berenson; Sven Bergmann; Hannah Blackburn; Eric Boerwinkle; Julie E Buring; Fabio Busonero; Harry Campbell; Stephen J Chanock; Wei Chen; Marilyn C Cornelis; David Couper; Andrea D Coviello; Pio d'Adamo; Ulf de Faire; Eco J C de Geus; Panos Deloukas; Angela Döring; George Davey Smith; Douglas F Easton; Gudny Eiriksdottir; Valur Emilsson; Johan Eriksson; Luigi Ferrucci; Aaron R Folsom; Tatiana Foroud; Melissa Garcia; Paolo Gasparini; Frank Geller; Christian Gieger; Vilmundur Gudnason; Per Hall; Susan E Hankinson; Liana Ferreli; Andrew C Heath; Dena G Hernandez; Albert Hofman; Frank B Hu; Thomas Illig; Marjo-Riitta Järvelin; Andrew D Johnson; David Karasik; Kay-Tee Khaw; Douglas P Kiel; Tuomas O Kilpeläinen; Ivana Kolcic; Peter Kraft; Lenore J Launer; Joop S E Laven; Shengxu Li; Jianjun Liu; Daniel Levy; Nicholas G Martin; Wendy L McArdle; Mads Melbye; Vincent Mooser; Jeffrey C Murray; Sarah S Murray; Michael A Nalls; Pau Navarro; Mari Nelis; Andrew R Ness; Kate Northstone; Ben A Oostra; Munro Peacock; Lyle J Palmer; Aarno Palotie; Guillaume Paré; Alex N Parker; Nancy L Pedersen; Leena Peltonen; Craig E Pennell; Paul Pharoah; Ozren Polasek; Andrew S Plump; Anneli Pouta; Eleonora Porcu; Thorunn Rafnar; John P Rice; Susan M Ring; Fernando Rivadeneira; Igor Rudan; Cinzia Sala; Veikko Salomaa; Serena Sanna; David Schlessinger; Nicholas J Schork; Angelo Scuteri; Ayellet V Segrè; Alan R Shuldiner; Nicole Soranzo; Ulla Sovio; Sathanur R Srinivasan; David P Strachan; Mar-Liis Tammesoo; Emmi Tikkanen; Daniela Toniolo; Kim Tsui; Laufey Tryggvadottir; Jonathon Tyrer; Manuela Uda; Rob M van Dam; Joyce B J van Meurs; Peter Vollenweider; Gerard Waeber; Nicholas J Wareham; Dawn M Waterworth; Michael N Weedon; H Erich Wichmann; Gonneke Willemsen; James F Wilson; Alan F Wright; Lauren Young; Guangju Zhai; Wei Vivian Zhuang; Laura J Bierut; Dorret I Boomsma; Heather A Boyd; Laura Crisponi; Ellen W Demerath; Cornelia M van Duijn; Michael J Econs; Tamara B Harris; David J Hunter; Ruth J F Loos; Andres Metspalu; Grant W Montgomery; Paul M Ridker; Tim D Spector; Elizabeth A Streeten; Kari Stefansson; Unnur Thorsteinsdottir; André G Uitterlinden; Elisabeth Widen; Joanne M Murabito; Ken K Ong; Anna Murray Journal: Nat Genet Date: 2010-12 Impact factor: 38.330
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Authors: Ken K Ong; Cathy E Elks; Shengxu Li; Jing Hua Zhao; Jian'an Luan; Lars B Andersen; Sheila A Bingham; Soren Brage; George Davey Smith; Ulf Ekelund; Christopher J Gillson; Beate Glaser; Jean Golding; Rebecca Hardy; Kay-Tee Khaw; Diana Kuh; Robert Luben; Michele Marcus; Michael A McGeehin; Andrew R Ness; Kate Northstone; Susan M Ring; Carol Rubin; Matthew A Sims; Kijoung Song; David P Strachan; Peter Vollenweider; Gerard Waeber; Dawn M Waterworth; Andrew Wong; Panagiotis Deloukas; Inês Barroso; Vincent Mooser; Ruth J Loos; Nicholas J Wareham Journal: Nat Genet Date: 2009-05-17 Impact factor: 38.330