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Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats.

Artikel i vetenskaplig tidskrift
Författare Cecilia Nilsson
Eva Jennische
Hoi-Por Ho
Elias Eriksson
Per Björntorp
Agneta Holmäng
Publicerad i European journal of endocrinology / European Federation of Endocrine Societies
Volym 146
Nummer/häfte 2
Sidor 251-60
ISSN 0804-4643
Publiceringsår 2002
Publicerad vid Hjärt-kärlinstitutionen
Institutionen för anatomi och cellbiologi
Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi
Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi
Sidor 251-60
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Adrenal Glands, anatomy & histology, physiology, Adrenocorticotropic Hormone, blood, Aging, Animals, Animals, Newborn, Corticosterone, blood, Female, Glucose Clamp Technique, Hippocampus, chemistry, physiology, Hypothalamus, chemistry, physiology, Insulin, blood, pharmacology, Lipopolysaccharides, administration & dosage, pharmacology, Motor Activity, Neurosecretory Systems, drug effects, physiology, Pregnancy, Progesterone, blood, Rats, Rats, Wistar, Receptors, Glucocorticoid, analysis, Salmonella enteritidis, Stress, Physiological, Testosterone, blood
Ämneskategorier Farmakologi och toxikologi

Sammanfattning

OBJECTIVES: 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. DESIGN: 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. CONCLUSION: 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.

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