PARATHYROID HORMONE-RELATED PROTEIN AND IMPLANTATION

描述：(改编自申请者S描述)甲状旁腺 激素相关蛋白(PTHrP)是一种最先从 与恶性体液高钙血症综合征相关的肿瘤。 甲状旁腺激素受体最近也在一些正常组织中被发现。 包括子宫内膜、子宫肌层和胎盘。研究表明， 结果表明，甲状旁腺激素相关蛋白由子宫蜕膜间质细胞表达。 小鼠子宫以及胚泡的滋养外胚层 用体外培养的小鼠囊胚刺激滋养层细胞生长。这个 研究人员推测，PTHrP在锚定中起着重要作用 着床过程中早期滋养层细胞的扩散 这一过程涉及刺猬信号蛋白的成员。 这项提案的具体目标是：确定PTHrP是否采取行动 通过刺激滋养层细胞的生成来促进滋养层细胞的生长 细胞外基质蛋白纤维连接蛋白或层粘连蛋白或调节表达 这些蛋白质的受体；以及PTHrP是否刺激 分泌特定的金属蛋白酶，包括明胶酶A和B。 检测发育中的小鼠囊胚和早期滋养层细胞 细胞表达刺猬信号蛋白及其受体的成员， PTHrP对胚泡发育的刺激作用是否包括 这条信号通路。

DESCRIPTION: (Adapted from the applicant s description) Parathyroid hormone-related protein (PTHrP) is a factor which was first isolated from tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP has also recently been identified in a number of normal tissues including the endometrium, myometrium and placenta. Studies have demonstrated that PTHrP is expressed by decidualized stromal cells in the mouse uterus as well as the trophectoderm of blastocysts and acts to stimulate trophoblast outgrowth by mouse blastocysts cultured in vitro. The researchers hypothesize that PTHrP plays an important role in the anchoring and spreading of early trophoblast cells during the process of implantation and that this process involves members of the hedgehog signalling proteins. The specific aims of this proposal are: To determine whether PTHrP acts to increase trophoblast outgrowth by stimulating production of the extracellular matrix proteins fibronectin or laminin or regulates expression of the receptors for these proteins; and whether PTHrP stimulates the secretion of specific metalloproteinases including gelatinases A and B. To determine whether the developing mouse blastocyst and early trophoblast cells express members of the hedgehog signaling proteins and their receptor, and whether the stimulatory effect of PTHrP on blastocyst outgrowth involves this signaling pathway.