Developmental Control of Plasma Leptin and Adipose Leptin Messenger Ribonucleic Acid in the Ovine Fetus during Late Gestation: Role of Glucocorticoids and Thyroid Hormones

Deirdre M. O'Connor, Dominique Blache, Nigel Hoggard, Emily Brookes, F. B. Peter Wooding, Abigail L. Fowden, Alison J. Forhead

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

In developed countries, the increasing incidence of obesity is a serious health problem. Leptin exposure in the perinatal period affects long-term regulation of appetite and energy expenditure, but control of leptin production in utero is unclear. This study investigated perirenal adipose tissue ( PAT) and placental leptin expression in ovine fetuses during late gestation and after manipulation of plasma glucocorticoid and thyroid hormone concentrations. Between 130 and 144 d of gestation ( term at 145 +/- 2 d), plasma leptin and PAT leptin mRNA levels increased in association with increments in plasma cortisol and T-3. Fetal adrenalectomy prevented these developmental changes, and exposure of intact 130 d fetuses to glucocorticoids, by cortisol infusion or maternal dexamethasone treatment, caused premature elevations in plasma leptin and PAT leptin gene expression. Fetal thyroidectomy increased plasma leptin and PAT leptin mRNA abundance, whereas intravenous T-3 infusion to intact 130 d fetuses had no effect on circulating or PAT leptin. Leptin mRNA expression was low in the ovine placenta. Therefore, in the sheep fetus, PAT appears to be a primary source of leptin in the circulation, and leptin gene expression is regulated by both glucocorticoids and thyroid hormones. Developmental changes in circulating and PAT leptin may mediate the maturational effects of cortisol in utero and have long-term consequences for appetite regulation and the development of obesity.
Original languageEnglish
Pages (from-to)3750-3757
Number of pages8
JournalEndocrinology
Volume148
Issue number8
Early online date10 May 2007
DOIs
Publication statusPublished - 1 Aug 2007

Keywords

  • OB gene-expression
  • cord blood leptin
  • fetal sheep
  • circulating leptin
  • intrauterine growth
  • RNA expression
  • body-weight
  • obese gene
  • near-term
  • tissue

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