Study of differention inducing factors on the differention of placental cells

胎盘在怀孕期间对胎儿和母亲都起着重要的作用。它把母亲的营养、氧气和激素输送给胎儿。对母亲来说，它提供了许多激素并改变了代谢状态。生殖器官的局部环境，特别是胎盘和子宫内膜，通过局部产生的生长因子、细胞因子和激素，以旁分泌或自分泌的方式相互交流。在此背景下，我们研究了这些物质如何调节滋养层细胞和子宫内膜细胞的生物学功能，并分析了生殖器官中产生的激素或物质的分子特征。首先，我们阐明了被称为分化诱导剂的维甲酸和抗坏血酸对滋养细胞中产生的维持妊娠早期不可或缺的绒毛膜促性腺激素的刺激作用。其次，在生殖器官，尤其是滋养细胞中，发现了甲状旁腺激素相关激素（PTHrP）的产生，PTHrP被称为恶性肿瘤体液性高钙血症的物质，是钙代谢的局部调节剂和生长因子。我们还检查了怀孕期间和胎儿血液中PTHrP的水平。提示PTHrP在维持母体和胎儿钙稳态中起重要作用。第三，研究子宫内膜细胞的生物功能（纤溶酶原激活剂系统）是如何被调节的。我们发现，在翻译前水平，phorbol酯、蛋白激酶C刺激剂和EGF刺激了子宫内膜细胞中组织型纤溶酶原拮抗剂和纤溶酶原抑制剂-1的产生。

Placenta plays important roles during pregnancy to the fetus and mother. To the fetus, it tranports nutrients, oxigen and hormones from The mother. To the mother, it provides many hormones and changes metabolic status. Local environment in the reproductive organs, especially in the placenta and endometrum communicate each other, via locally produced growth factors, cytokaines and hormones, in the paracrine or autocrine manner. In this context, we examined how these substances modulates the biological functions of the trophoblastic cells as well as endometrial cells, and analyzedz the molecular characters of hormones or substances produced in the reproductive organs.First, we clarified the stimulatory effect of retinoic acid, known as differentiation inducer, and ascorbic acid on human chorionic gonadotropin, indispensable to maintain the early stage of pregnancy, produced in the trophoblastic cells.Second, production of parathyroid hormone-related hormone(PTHrP), known as the substance causing humoral hyper calcemia of malignancy, local regulator of calcium metabolism and growth factor, was demonstrated in the reproductive organs, especially in the trophoblastic cells. We also examined the blood PTHrP levels during pregnancy and in the fetus. The results suggest that PTHrP plays important roles to maintain the calcium homeostasis in the environment of mother and fetus.Third, how the biological function(plasminogen activator system)of endometrial cells is modulated was examined. We showed that phorbol ester, protein kinase C stimulator, and EGF stimulated the tissue-type plasminogen antivator production as well as plsminogen inhibitor-1 production at the pretranslational level in the endometrial cells.