Steroid-dependent up-regulation of adipose leptin secretion in vitro during pregnancy in mice

Circulating leptin levels are elevated during the later stages of pregnancy in mammals, suggesting that maternal leptin may play a role in maintenance of pregnancy and/or preparation for parturition and lactation. The regulat ion and source of circulating leptin during pregnancy remains undetermined, but leptin mRNA levels increase in adipose tissue during this time in some species. Considerable controversy exists whether placenta is also a leptin secreting tissue during pregnancy. Here, we directly demonstrate that lept in secretion rates from mouse adipose tissue in vitro are decreased during early pregnancy and up-regulated during late pregnancy and lactation. Chang es in leptin secretion rates in vitro paralleled those of circulating lepti n in vivo during gestation. Subcutaneous implants of estradiol or corticost erone into lactating mice for 48 h stimulated adipose leptin secretion rate s in vitro to the level of that in pregnant mice. However, corticosterone, but not estradiol, increased leptin secretion when added to isolated adipos e tissue in vitro. Placentae obtained at two stages of pregnancy did not se crete leptin in vitro, either when acutely isolated or when dissociated int o cells for long-term cultures. Placental tissue (or cells) secreted proges terone, however, demonstrating placental viability. We conclude that hyperl eptinemia during late pregnancy in mice primarily results from corticostero ne-dependent up-regulation of leptin secretion from adipose tissue, and tha t the placenta does not contribute to leptin secretion. The initial decreas e in leptin secretory rates from adipose tissue during early pregnancy may facilitate energy storage for the subsequent, increased metabolic demands o f later pregnancy and lactation.