title: Differential Effects of Alcohol on Excitatory and Inhibitory Puberty-Related Peptides in the Basal Hypothalamus of the Female Rat.
abstract: 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.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Srivastava
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas.
authors.forename: Jill K
authors.initials: JK
authors.lastname: Hiney
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas.
authors.forename: Kristyn
authors.initials: K
authors.lastname: Stevener
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas.
authors.forename: William L
authors.initials: WL
authors.lastname: Dees
mesh_terms: D000818:Animals; D004399:Dynorphins / Q000096:biosynthesis; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D059648:Kisspeptins / Q000096:biosynthesis*; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000008:administration & dosage / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*
chemical_list: C491406:Kiss1 protein, rat; D059648:Kisspeptins; C578027:Lin28A protein, rat; D016601:RNA-Binding Proteins; D000431:Ethanol; D004399:Dynorphins
keywords: Alcohol; Dynorphin; Kisspeptin; Lin28b; Puberty