Leptin is a polypeptide hormone produced by adipose and other endocrine tissues. Although it has been linked to receptormediated pathways that directly influence human conceptus development, mechanisms that regulate the leptin receptor in pregnancy-specific tissues remain unclear. Therefore, we assessed leptin-receptor ontogeny and regulation in the baboon (Papio sp.), a primate model for human pregnancy. Placentae, decidua, and amniochorion were collected from baboons in early (Days 54-63, n

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... ‬ 4), mid (Days 98-103, n ‫؍‬ 4), and late (Days 159-165, n ‫؍‬ 4) gestation. Regulation by estrogen was assessed by elimination of androgen precursors via removal of the fetus (fetectomy) at midgestation and collection of tissues in late gestation (n ‫؍‬ 4; term, ϳ184 days). Maternal serum was sampled with advancing gestation, and the abundance of soluble leptin receptor (solLepR), a potential mediator of gestational hyperleptinemia, was determined. Two placental leptin-receptor isoforms (130 and 150 kDa) increased (P Ͻ 0.04 and P Ͻ 0.02, respectively) in abundance with advancing gestation. Similarly, the 130-kDa isoform increased approximately fourfold (P Ͻ 0.0025) in decidua and approximately 10-fold (P Ͻ 0.015) in amniochorion between early and late gestation. Following fetectomy, maternal serum estradiol levels declined approximately 85% (P Ͻ 0.03), and the 150-kDa placental leptin-receptor isoform was reduced by more than half (P Ͻ 0.002). Maternal serum solLepR concentrations were correlated with gestational age (r ‫؍‬ 0.52, P Ͻ 0.01) and were unaffected by fetectomy. The presence of leptin-receptor isoforms in pregnancy-specific tissues further denoted leptin's potential to directly influence conceptus development, whereas the 130-kDa solLepR identified in maternal serum suggested a means to facilitate the hyperleptinemia typical of primate pregnancy. Although estrogen did not appear to be the principal regulator of solLepR, it and other factors linked to advancing gestation may be implicated in the regulation of leptin-receptor synthesis. conceptus, estrogen, leptin, leptin receptor, pregnancy