Pregnancy

Effects of Leptin on Fetal Plasma Adrenocorticotropic Hormone and Cortisol Concentrations and the Timing of Parturition in Sheep

Abstract
We have investigated whether leptin can suppress the prepartum activation of the fetal HPA axis and delay the timing of parturition in the sheep. Firstly, we investigated the effects of a 4 day intravascular infusion of recombinant ovine leptin (n=7) or saline (n=6) on fetal plasma ACTH and cortisol concentrations, starting from 136 days (d) gestation, ie 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 d 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 136/7 and 140/1 d 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 d gestation, there was no effect of a 4-5 fold increase in circulating leptin on fetal ACTH concentrations. In contrast, leptin infusion from 144 d 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 d; leptin infused, 149.8 ± 1.0 d). In saline infused fetuses, there was a significant negative relationship between the plasma concentrations of cortisol (y) and leptin (x) between 138 and 146 d 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.

Key words: Pregnancy • Adrenal • Cortisol • Leptin

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