Regulation of leptin and leptin receptor in baboon pregnancy: Effects of advancing gestation and fetectomy

Leptin, a product of both adipose tissue and the placental syncytiotrophobl ast and a potential regulator of primate conceptus development, increases i n the maternal circulation with advancing gestation. This increase may-be p otentiated by estrogens, which also increase as pregnancy progresses. In th e present study adipose tissue was collected from nonpregnant (n = 5) baboo ns (Papio sp) and in baboons during early (days 58-62; n = 5), mid (days 98 -102; n = 5), and late (days 158-162; n = 5) pregnancy (term, similar to 18 4 days). Additionally, placental estrogen production was inhibited in pregn ant baboons by the removal of fetal androgen precursors via fetectomy at mi dgestation, with tissues collected from fetectomized (n = 5) baboons approx imately 60 days later. Leptin, estrogens, and androgens were quantitated in maternal serum by RIA. Leptin (LEP) and leptin receptor (LEP-R, and LEP-R, isoforms) messenger ribonucleic acids (mRNAs) were quantitated by competit ive RT-PCR, and leptin concentrations were determined by RIA in maternal ad ipose and placental villous tissues. Although LEP transcript abundance in a dipose tissues was un-changed as a result of pregnancy or with advancing ge station, the leptin protein level was higher (P < 0.02) in pregnant baboons in early gestation than in nonpregnant baboons and increased with gestatio nal age (P < 0.04). Maternal serum estrogens (estradiol and estrone) and an drogens (androstenedione and testosterone) were lower (P < 0.0001) in fetec tomized baboons than in intact controls. Serum leptin concentrations were u nchanged by fetectomy, but the abundance of LEP mRNA transcripts was lower (P < 0.003) in sc adipose tissue and 3-fold higher (P < 0.05) in placenta. Similarly, the leptin protein level declined (P < 0.05) in sc adipose tissu e and increased (P < 0.05) in placenta in fetectomized baboons. Although LE P-R, mRNA levels were unchanged after fetectomy, placental LEP-R, transcrip t abundance was lower (P < 0.04) than in pregnancy-intact baboons matched f or gestational age. Results suggest that both adipose tissue and the placen ta may contribute to maternal hyperleptinemia during normal primate pregnan cy. Furthermore, the withdrawal of placental steroids results in the enhanc ed placental leptin production that is commensurate with a decline in produ ction by sc adipose tissue.