Pregnancy

Two Isoforms of the Leptin Receptor Are Enhanced in Pregnancy-Specific Tissues and Soluble Leptin Receptor Is Enhanced in Maternal Serum with Advancing Gestation in the Baboon

Abstract
Leptin is a polypeptide hormone produced by adipose and other endocrine tissues. Although it has been linked to receptor-mediated 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 = 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 ~ 184 days. Maternal serum was sampled with advancing gestation, and the abundance of soluble leptin receptor (solLepR), a potential mediator of gestational hyperleptinemia, determined. Two placental leptin receptor isoforms (130 kDa, 150 kDa) increased (P < 0.04 and P < 0.02, respectively) in abundance with advancing gestation. Similarly, the 130 kDa isoform increased ~ 4-fold (P < 0.0025) in decidua and ~ 10-fold (P < 0.015) in amniochorion between early and late gestation. Following fetectomy, maternal serum estradiol levels declined ~ 85% (P < 0.03) and the 150 kDa placental leptin receptor isoform was reduced by greater than one-half (P < 0.002). Maternal serum solLepR concentrations were correlated with gestational age (r = 0.52, P < 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, while 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.

Key words: Pregnancy • Conceptus • Leptin • Leptin receptor • Placenta

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