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Pregnancy |
Departments of Physiology3
Obstetrics and Gynaecology,4 University of Adelaide, Adelaide,South Australia 5005, Australia
Academic Division of Child Health,5 University of Nottingham, Nottingham, NG7 2UH, United Kingdom
Department of Animal Sciences,6 University of Missouri, Columbia, Missouri 65211
Department of Physiology,7 University of New England, Armidale, New South Wales 2350, Australia
We investigated whether leptin can suppress the prepartum activation of the fetal hypothalamus-pituitary-adrenal (HPA) axis and delay the timing of parturition in the sheep. First, we investigated the effects of a 4-day intravascular infusion of recombinant ovine leptin (n = 7) or saline (n = 6) on fetal plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations, starting from 136 days gestation (i.e., at the onset of the prepartum activation of the fetal HPA axis. The effects of a continuous intrafetal infusion of leptin (n = 7) or saline (n = 5) from 144 days gestation on fetal plasma ACTH and cortisol concentrations and the timing of delivery were also determined in a separate study. There was an increase in fetal plasma ACTH (P < 0.01) and cortisol (P < 0.001) concentrations when saline was infused between 136–137 and 140–141 days gestation. Plasma ACTH and cortisol concentrations did not rise, however, when leptin was infused during this period of gestation. When leptin was infused after 144 days gestation, there was no effect of a 4- to 5-fold increase in circulating leptin on fetal ACTH concentrations. In contrast, leptin infusion from 144 days gestation suppressed (P < 0.05) fetal plasma cortisol concentrations by around 40% between 90 and 42 h before delivery. There was no difference, however, in the length of gestation between the saline- and leptin-infused groups (saline infused, 150.2 ± 0.5 days; leptin infused, 149.8 ± 1.0 days). In saline-infused fetuses, there was a significant negative relationship between the plasma concentrations of cortisol (y) and leptin (x) between 138 and 146 days gestation (y = 81.4 – 7.7x, r = 0.38, P < 0.005). This study provides evidence for an endocrine negative feedback loop between leptin and the HPA axis in fetal life.
2 Correspondence: I.C. McMillen, Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia. FAX: 61 8 8 303 3356;caroline.mcmillen{at}adelaide.edu.au
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