title: Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats.
abstract: OBJECTIVE
  Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood.
  
  
  METHODS
  Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth.
  
  
  RESULTS
  Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity (P<0.05), measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS-treated rats were elevated (P<0.05), as were corticosterone levels after exposure to a novel environment stress (P<0.05). The adrenals were morphologically changed and enlarged (P<0.05) in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats (P<0.05). Furthermore, circulating progesterone levels were lower (P<0.05) and testosterone tended to be higher.
  
  
  CONCLUSIONS
  The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.
authors.affiliation: Department of Heart and Lung Diseases, Goteborg University, Goteborg, Sweden. Cecilia.Nilsson@wlab.wall.gu.se
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nilsson
authors.forename: Eva
authors.initials: E
authors.lastname: Jennische
authors.forename: Hoi-Por
authors.initials: HP
authors.lastname: Ho
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Per
authors.initials: P
authors.lastname: Bjorntorp
authors.forename: Agneta
authors.initials: A
authors.lastname: Holmang
mesh_terms: D000311:Adrenal Glands / Q000033:anatomy & histology / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D007031:Hypothalamus / Q000737:chemistry / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000032:analysis; D012477:Salmonella enteritidis; D013312:Stress, Physiological; D013739:Testosterone / Q000097:blood
chemical_list: D007328:Insulin; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D013739:Testosterone; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone