Effects of estrogen on leptin receptor and binding properties of the soluble leptin receptor isoform in baboon pregnancy
Description
Leptin, the protein product of the LEP gene, regulates energy homeostasis and metabolism by inducing satiety. Therefore, the gestational hyperleptinemia associated with primate pregnancy is counterintuitive. A soluble isoform of the leptin receptor (solLepR) is proposed to aid in the maintenance of serum leptin concentrations. Thus, solLepR may sequester leptin in maternal serum and prevent its clearance, thereby contributing to gestational hyperleptinemia. Estrogen is a candidate in the regulation of leptin receptor production. Furthermore, the placenta is indicated as a source of both solLepR and other leptin receptor isoforms. Therefore, we hypothesize that elevated maternal estrogen levels present during primate pregnancy function to enhance not only leptin receptor biosynthesis in pregnancy-specific tissues, but also production of the solLepR, thereby increasing the leptin-binding activity of pregnancy serum We used the baboon (Papio sp.), a well characterized model of human pregnancy, to evaluate the impact of maternal estrogen on leptin receptor production from the placenta, decidua, and amniochorion. A 130 kDa isoform of the leptin receptor increased with advancing gestation in all tissues. Additionally, a 150 kDa placental isoform was detected. To examine the impact of estrogen on receptor production, maternal estrogen availability was reduced, via fetectomy, and then substantially restored following fetectomy, via estradiol supplementation. Placental transcripts for a short isoform of the receptor decreased in abundance following fetectomy. Likewise, protein abundance for the 130 kDa isoform declined following estrogen supplementation in both placenta and decidua An index of leptin-binding capacity in pregnancy serum was obtained by evaluating solLepR abundance. solLepR increased with advancing gestation, indicating elevated leptin-binding capacity. Furthermore, the decrease in solLepR abundance following estrogen supplementation coincides with the decline in the 130 kDa placental and decidual isoform, perhaps indicating these tissues as pregnancy-specific sources of solLepR. The leptin-binding capacity of pregnancy serum appeared unaltered by fetectomy or estrogen treatment Collectively, results suggest that while estrogen is not a direct positive regulator of leptin receptor production, a complex interplay between maternal estrogen availability and gestational factors influences receptor production from pregnancy-specific tissues. This production has the ability to impact the leptin-binding capacity of pregnancy serum, via solLepR