title: Effects of ethanol on leptin secretion and the leptin-induced luteinizing hormone (LH) release from late juvenile female rats.
abstract: BACKGROUND
  Chronic ethanol (EtOH) exposure lowers serum insulin-like growth factor-1 (IGF-1) and luteinizing hormone (LH) levels and also delays female puberty, similar to the deficits in the reproductive system that occur during leptin deficiency. Leptin administration restores fertility and gonadotropin secretion in the ob/ob mouse and can induce recovery of reproductive function in food-restricted animals. This study assessed the effects of EtOH on serum leptin levels, and whether exogenous leptin administration could restore IGF-1 and LH levels in the EtOH-treated animals.
  
  
  METHODS
  In the first study, 29-day-old female rats were divided into control and EtOH-treated groups, each of which received their respective diet regimen for 5 consecutive days. The EtOH-treated animals were subdivided and received an intraperitoneal injection of either leptin (100 microg/0.1 ml) or saline twice daily. Control animals also received intraperitoneal saline injections twice daily. On day 34, animals were killed, and serum leptin, LH, and IGF-1 were measured by RIA. In a second study we assessed the acute effects of a single 3 g/kg dose of EtOH on the ability of leptin to act centrally to induce LH release. For this, leptin (1 microg) was administered via a third ventricular (3V) cannula and blood sampling via jugular cannula. In a third experiment, animals were again subjected to a chronic feeding regimen. When 34 days old, they were killed and the anterior pituitaries removed and incubated in a static incubation system for 60 min to establish basal LH release, then for an additional 60 min in medium containing leptin (10(-7) M).
  
  
  RESULTS
  Chronic EtOH exposure lowered serum leptin (p < 0.01), IGF-1 (p < 0.01), and LH (p < 0.05) levels. Leptin administration to EtOH-treated animals did not restore serum IGF-1 levels. This peptide did, however, effectively restore LH levels to normal, but did not advance the timing of puberty. Acute EtOH administration was found to block leptin-induced LH release following central administration of the peptide. Conversely, anterior pituitaries from control and 5-day EtOH-treated animals that were incubated in vitro released (p < 0.01) equal amounts of LH in response to leptin (10(-7) M).
  
  
  CONCLUSIONS
  These data demonstrate that EtOH administration not only can suppress peripheral levels of leptin, but also blocks its central action to facilitate LH secretion. Although replacement of leptin can reverse the EtOH-induced suppression of LH by a direct action at the level of the pituitary, it cannot elevate serum IGF-1; a peripheral signal that acts centrally to stimulate LH releasing-hormone (LHRH)/LH release during the juvenile-peripubertal transition period, and thus accelerates the initiation of female puberty. These results demonstrate further the complex actions and interactions of multiple hormones involved in the pubertal process and the vulnerability of their actions to the toxic effects of EtOH.
authors.affiliation: Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A & M University, College Station 77843-4458, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Hiney
authors.forename: R K
authors.initials: RK
authors.lastname: Dearth
authors.forename: F
authors.initials: F
authors.lastname: Lara
authors.forename: S
authors.initials: S
authors.lastname: Wood
authors.forename: V
authors.initials: V
authors.lastname: Srivastava
authors.forename: W
authors.initials: W
authors.lastname: Les Dees
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D020738:Leptin; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone