Green K E, Thota C, Hankins G D V, Yallampalli C, Dong Yuan-Lin
Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1062, USA.
Mol Hum Reprod. 2006 Jul;12(7):443-50. doi: 10.1093/molehr/gal053. Epub 2006 Jun 13.
Calcitonin gene-related peptide (CGRP) is a multifunctional peptide present in both maternal and fetal circulations in pregnancy. Its receptors have been identified on human trophoblast cells, but the role of CGRP in trophoblast differentiation remains unknown. This study was designed to determine the effect of CGRP on the differentiation of villous trophoblasts isolated from normal human term placentae. The morphological and functional differentiation of the trophoblast cells were assessed by desmosomal protein immunofluorescent staining and the quantification of hCG, estrogen and progesterone secretion. Results showed that (i) exposure of villous trophoblast cells to CGRP led to a dose-dependent increase in intracellular cyclic adenosine monophosphate (cAMP) accumulation; (ii) immunofluorescent staining with antidesmosomal antibody was identified at the boundaries between aggregated cytotrophoblast cells, and these stainings disappeared when cells fused to form syncytiotrophoblast cells; (iii) the formation of multinucleated syncytiums in primary cultured cytotrophoblasts was stimulated by CGRP as evidenced by the changes in antidesmosomal staining; (iv) CGRP increases trophoblast hCG secretion in a time- and dose-dependent manner, and this secretion was blocked by CGRP antagonist, CGRP(8-37), and (v) both 17beta-estradiol (E(2)) and progesterone concentrations in the culture medium were increased by CGRP, and these increases were dose dependent. These observations suggest that CGRP may be involved in the morphological and functional differentiation of trophoblast cells, and these actions might be attributed to CGRP-induced intracellular cAMP accumulation.
降钙素基因相关肽（CGRP）是一种多功能肽，存在于孕期母体和胎儿的循环系统中。已在人滋养层细胞上鉴定出其受体，但CGRP在滋养层细胞分化中的作用尚不清楚。本研究旨在确定CGRP对从正常足月人胎盘分离的绒毛滋养层细胞分化的影响。通过桥粒蛋白免疫荧光染色以及人绒毛膜促性腺激素（hCG）、雌激素和孕酮分泌的定量分析来评估滋养层细胞的形态和功能分化。结果显示：（i）绒毛滋养层细胞暴露于CGRP会导致细胞内环状单磷酸腺苷（cAMP）积累呈剂量依赖性增加；（ii）用抗桥粒抗体进行免疫荧光染色可在聚集的细胞滋养层细胞之间的边界处观察到，当细胞融合形成合体滋养层细胞时这些染色消失；（iii）CGRP刺激原代培养的细胞滋养层细胞形成多核合体，这可通过抗桥粒染色的变化得到证实；（iv）CGRP以时间和剂量依赖性方式增加滋养层细胞hCG分泌，且这种分泌被CGRP拮抗剂CGRP（8 - 37）阻断；（v）CGRP使培养基中的17β - 雌二醇（E₂）和孕酮浓度均升高，且这些升高呈剂量依赖性。这些观察结果表明，CGRP可能参与滋养层细胞的形态和功能分化，且这些作用可能归因于CGRP诱导的细胞内cAMP积累。
