Maternal ghrelin plays an important role in rat fetal development during pregnancy
Maternal ghrelin plays an important role in rat fetal development during pregnancy
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DOI：
10.1210/en.2005-0708
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
Murakami, N
中科院分区：
文献类型：
--
作者：
Nakahara, K;Nakagawa, M;Murakami, N
Ghrelin是一种内源性GH促分泌素受体（GH secretagogue receptor，GHS-R）配体，最初从大鼠和人胃中分离得到。在这项研究中，我们报告的关键作用，母体生长激素释放肽在胎儿发育。高水平的生长激素释放肽受体（GHS-R）的mRNA检测到各种外周胎儿组织开始在胚胎d 14和持续到出生。胎儿GHS-R的表达也证实了胎儿组织的免疫组织化学。放射自显影显示去酰基生长素释放肽和酰基生长素释放肽都与胎儿组织结合。长期治疗的母亲与生长激素释放肽导致出生体重显着增加相比，新生儿从盐水治疗的母亲。即使在ghrelin治疗后通过配对喂养限制母体食物摄入，仍然发生对胎儿发育的显著刺激。相反，母亲主动免疫生长激素释放肽降低胎儿体重在怀孕期间。一个单一的生长激素释放肽注射到母亲增加循环生长激素释放肽水平在5分钟内的胎儿注射，这表明母体生长激素释放肽容易过渡到胎儿的循环。在胎儿血液和羊水中检测到高水平的去酰基生长素释放肽。酰化和脱酰基ghrelin均以剂量依赖性方式增加培养的胎儿皮肤细胞的[H-3]胸苷和5-溴-2 '-脱氧尿苷掺入，钙成像分析显示，酰基和脱酰基ghrelin分别增加离散培养的胎儿皮肤细胞中的Ca 2+内流。这些结果表明，母体生长激素释放肽在妊娠后期调节胎儿发育。
Ghrelin, an acylated peptide serving as an endogenous ligand for GH secretagogue receptor (GHS-R), was originally isolated from rat and human stomach. In this study, we report the critical role of maternal ghrelin in fetal development. High levels of ghrelin receptor (GHS-R) mRNA were detected in various peripheral fetal tissues beginning at embryonic d 14 and lasting until birth. Fetal GHS-R expression was also confirmed in fetal tissues by immunohistochemistry. Autoradiography revealed that both des-acyl ghrelin and acyl ghrelin bind to fetal tissues. Chronic treatment of mothers with ghrelin resulted in a significant increase in birth weight in comparison to newborns from saline-treated mothers. Even when maternal food intake after ghrelin treatment was restricted through paired feeding, significant stimulation of fetal development still occurred. Conversely, active immunization of mothers against ghrelin decreased fetal body weight during pregnancy. A single ghrelin injection into the mother increased circulating ghrelin levels in the fetus within 5 min of injection, suggesting that maternal ghrelin transits easily to the fetal circulation. High levels of des-acyl ghrelin were detected in fetal blood and amniotic fluid. Both acylated and des-acyl ghrelin increased [H-3] thymidine and 5-bromo-2'-deoxyuridine incorporation of cultured fetal skin cells in a dose-dependent manner, and calcium-imaging analysis revealed that acyl and des-acyl ghrelin increased the Ca2+ influx in discrete cultured fetal skin cells, respectively. These results indicate that maternal ghrelin regulates fetal development during the late stages of pregnancy.