title: Short-term alcohol administration alters KiSS-1 gene expression in the reproductive hypothalamus of prepubertal female rats.
abstract: BACKGROUND
  Kisspeptins bind to the G-protein-coupled receptor (GPR54) to activate hypothalamic luteinizing hormone releasing hormone (LHRH) secretion at the time of puberty. Alcohol (ALC) causes depressed prepubertal LHRH release, resulting in depressed luteinizing hormone (LH) secretion and delayed puberty. Because KiSS-1 and GPR54 are important to the onset of puberty, we assessed the effects of chronic ALC administration on basal expression of these puberty-related genes within the reproductive hypothalamus, as well as hormones and transduction signaling pathways contributing to their activity.
  
  
  METHODS
  Immature female rats were fed a liquid diet containing ALC for 6 days beginning when 27 days old. Controls received either companion isocaloric liquid diet or rat chow and water. Animals were decapitated on day 33, in the late juvenile stage of development. Blood was collected for the assessment of serum hormone levels. Brain tissues containing the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei were obtained for assessing expression of specific puberty-related genes and proteins.
  
  
  RESULTS
  KiSS-1 mRNA levels in the AVPV and ARC nuclei were suppressed (p < 0.001) in the ALC-treated rats. GPR54 gene and protein expressions were both modestly increased (p < 0.05) in AVPV nucleus, but not in ARC nucleus. Alcohol exposure also resulted in suppressed serum levels of insulin-like growth factor-1 (IGF-1), LH, and estradiol (E(2)). As IGF-1, in the presence of E(2), can induce expression of the KiSS-1 gene, we assessed the potential for ALC to alter IGF-1 signaling in the reproductive hypothalamus. IGF-1 receptor gene and protein expressions were not altered. However, protein expression of phosphorylated Akt, a transduction signal used by IGF-1, was suppressed in the AVPV (p < 0.05) and ARC (p < 0.01) nuclei.
  
  
  CONCLUSIONS
  Alcohol causes suppressed KiSS-1 gene expression in the reproductive hypothalamus; hence, contributing to this drug's ability to cause suppressed LHRH secretion and disruption of the pubertal process. We suggest that this action, at least in part, is through altered IGF-1 signaling.
authors.affiliation: Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4458, USA.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Srivastava
authors.forename: Jill K
authors.initials: JK
authors.lastname: Hiney
authors.forename: W Les
authors.initials: WL
authors.lastname: Dees
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000097:blood; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000187:drug effects* / Q000235:genetics*
chemical_list: D002492:Central Nervous System Depressants; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D011506:Proteins; D000431:Ethanol; D004958:Estradiol; D012313:RNA; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone