Shanghai First Maternity and Infant Health Hospital, Tongji University, Shanghai 200040, People's Republic of China.
Reproduction. 2011 Aug;142(2):369-75. doi: 10.1530/REP-11-0053. Epub 2011 May 11.
Leptin produced by the placental syncytiotrophoblasts participates in a number of processes in pregnancy including implantation, proliferation of the cytotrophoblasts, and nutrient transfer across the placenta. Despite the functional significance of leptin in pregnancy, the regulation of leptin synthesis is poorly understood in human placental syncytiotrophoblasts. In this study, we investigated the role of endogenous human chorionic gonadotropin (hCG) in the regulation of leptin production as well as the underlying mechanism involving the cross talk between cAMP and p38 mitogen-activated protein kinase (MAPK) pathways. We found that neutralization of endogenous hCG with its antibody dose dependently decreased leptin mRNA level and secretion, whereas exogenous hCG increased leptin mRNA level and secretion. Activation of the cAMP pathway with dibutyryl cAMP (db cAMP) or forskolin recapitulated the stimulatory effect of hCG on leptin expression. Inhibition of protein kinase A with H89 not only reduced the basal leptin expression but also attenuated the induced leptin expression by hCG. Treatment of the syncytiotrophoblasts with db cAMP and hCG phosphorylated p38 MAPK. Inhibition of p38 MAPK with SB203580 not only reduced the basal leptin production but also attenuated the leptin-induced production by both hCG and db cAMP. These data suggest that endogenous hCG plays a significant role in maintaining leptin production in human placental syncytiotrophoblasts, and this effect involves a cross talk between cAMP and p38 MAPK pathways.
胎盘合体滋养层细胞产生的瘦素参与了妊娠过程中的许多过程，包括着床、滋养层细胞的增殖和营养物质穿过胎盘的转移。尽管瘦素在妊娠中的功能意义重大，但人类胎盘合体滋养层细胞中瘦素合成的调节机制还知之甚少。在这项研究中，我们研究了内源性人绒毛膜促性腺激素（hCG）在调节瘦素产生中的作用以及涉及 cAMP 和 p38 丝裂原活化蛋白激酶（MAPK）途径交叉对话的潜在机制。我们发现，用其抗体中和内源性 hCG 会剂量依赖性地降低瘦素 mRNA 水平和分泌，而外源性 hCG 则增加瘦素 mRNA 水平和分泌。用二丁酰环腺苷酸（db cAMP）或佛波酯激活 cAMP 途径可再现 hCG 对瘦素表达的刺激作用。用 H89 抑制蛋白激酶 A 不仅降低了基础瘦素表达，而且减弱了 hCG 诱导的瘦素表达。用 db cAMP 和 hCG 处理合体滋养层细胞可使 p38 MAPK 磷酸化。用 SB203580 抑制 p38 MAPK 不仅降低了基础瘦素的产生，而且减弱了 hCG 和 db cAMP 诱导的瘦素产生。这些数据表明，内源性 hCG 在维持人胎盘合体滋养层细胞瘦素产生中发挥重要作用，这种作用涉及 cAMP 和 p38 MAPK 途径之间的交叉对话。
