The late gestation increase in circulating ACTH and cortisol in the fetal sheep is suppressed by intracerebroventricular infusion of recombinant ovine leptin.
The obese gene product leptin, originally characterised as an adipocyte hormone coordinating the behavioural and neuroendocrine responses to starvation, is expressed in fetal adipocytes and placental trophoblast cells and is present in the fetal circulation. Concentrations of leptin in fetal blood correlate with fetal bodyweight and fat mass. In post-natal life, leptin conveys information about calorie intake and the state of adipose tissue energy stores, and plasma leptin levels are generally inversely correlated with hypothalamo-pituitary adrenal (HPA) activity. Late fetal life is characterised by increasing HPA activity that prepares the fetus for extrauterine life and initiates the endocrine cascade leading to parturition. We have investigated the hypothesis that leptin in the fetal circulation can inhibit the fetal HPA axis, thereby providing a mechanism by which the fetus can determine the fine timing of parturition as long as it is adequately nourished and growing appropriately. Here we show that a 5-day intracerebroventricular infusion of leptin to the sheep fetus in late gestation inhibits the pre-parturient rise in ACTH and cortisol concentrations, and that this seems to be a centrally mediated effect.
Howe
D C
DC
Department of Obstetrics and Gynaecology, The Queen Mother's Hospital, Yorkhill, Glasgow G3 8SJ, UK. HOWEdavidc@aol.com
Gertler
A
A
Challis
J R G
JR
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001127:Arginine Vasopressin; D001786:Blood Glucose / Q000378:metabolism; D002552:Cerebral Ventricles; D003346:Corticotropin-Releasing Hormone; D003864:Depression, Chemical; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005333:Fetus / Q000187:drug effects*; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011994:Recombinant Proteins; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone