| Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring. | |
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MedLine Citation:
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PMID: 11581014 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension. OBJECTIVE: To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the early-growth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations. DESIGN AND METHODS: Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography. RESULTS: Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited significant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring. CONCLUSIONS: The rat model of maternal dexamethasone treatment is established as a paradigm of 'programmed' hypertension in man. Our data show modification of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive fetal exposure to glucocorticoids could be a common early-life stimulus to the association between hyperinsulinaemia, hypertension and hyperleptinaemia often seen in individuals of low birthweight. |
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Authors:
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M C Sugden; M L Langdown; M J Munns; M J Holness |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of endocrinology / European Federation of Endocrine Societies Volume: 145 ISSN: 0804-4643 ISO Abbreviation: Eur. J. Endocrinol. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-02 Completed Date: 2001-12-04 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9423848 Medline TA: Eur J Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 529-39 Citation Subset: IM |
Affiliation:
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Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London, UK. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Weight / drug effects Carrier Proteins / metabolism* Dexamethasone / pharmacology* Dose-Response Relationship, Drug Eating / drug effects Embryonic and Fetal Development / drug effects Female Fetal Growth Retardation / complications Fetus / physiology* Glucocorticoids / pharmacology* Hypertension / chemically induced, complications Insulin / blood Leptin / antagonists & inhibitors, blood, metabolism* Male Organ Size / drug effects Placenta / anatomy & histology, drug effects, physiology* Pregnancy Pregnancy, Animal / physiology* Prenatal Exposure Delayed Effects* Rats Rats, Wistar Receptors, Cell Surface* Receptors, Leptin Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Glucocorticoids; 0/Leptin; 0/Receptors, Cell Surface; 0/Receptors, Leptin; 11061-68-0/Insulin; 50-02-2/Dexamethasone |
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