HORMONAL CONTROL OF FEMALE REPRODUCTIVE TRACT

这项研究旨在增加我们对 介导类固醇作用的基质-上皮相互作用， 生殖道 我们的研究重点是监管和 特定的生长因子的影响，并对特定的酶称为 基质金属蛋白酶（MMP）。 我们的研究在 三个主要领域。 首先，我们描述了两种新的形式， 肝细胞生长因子（HGF）在猕猴子宫内膜中表达。 这两个截短的HGF转录本类似于两个变体 (HGF/NK 1和HGF/NK 2）。 雌二醇处理的显微切割的总RNA的北方印迹 子宫内膜显示HGF/SF mRNA的表达比正常子宫内膜高10倍， 功能区的水平高于基底区。 原位 杂交证实了这种表达梯度，并表明， 特异性信号仅限于上皮下和血管周围 基质细胞 第二，我们用免疫细胞化学方法定位了 两种形式的血管内皮生长因子（VEGF）受体， 猕猴子宫内膜中的I型（FLT 1）和II型（flk 1/KDR）。 FLT1 在小血管的内皮表面上检测到染色， 大螺旋动脉的肌肉。 动脉染色最强的是 用雌二醇加孕酮（E2 + P）处理的猴子，表明 VEGF可能在黄体期动脉生长中发挥作用。 KDR 染色在血管内皮细胞中也是明显的。 然而，在这方面， 当P在周期结束时被撤回时，一波强劲的KDR 在上功能肌的基质细胞中观察到染色 区 基质细胞中的KDR可能在重塑中起作用 月经周期结束时的子宫内膜。 第三，关键 需要停药一段时间才能诱发月经。 我们有 评估各种基质金属蛋白酶（MMPs）的表达 在关键时期和之后。 当P被替换时， MMP-1、MMP-2、MMP-3和TIMP-1的表达在肿瘤发生的关键时期， 被挡出. 然而，当P在临界期之后被替换时，一些 但并非所有MMP都被阻断。 这表明MMP在两个方面都不同， 它们对磷抑制的敏感性及其在 月经 资助NIH HD 19182出版物Lindsey JS，Brenner RM. 恒河猴子宫内膜表达两种新的转录本， 肝细胞生长因子/分散因子。 第58章：一个人的世界（1） （摘要324）。 Lindsey JS，Slayden OD，Brenner RM. 纬向梯度 恒河猴肝细胞生长因子/分散因子表达的研究 猕猴子宫内膜 Mol Biol Cell 9：477 a，1998（摘要）。 Ruelle-Owen LA，Slayden OD，Matrisian LM，Brenner RM. 矩阵 猕猴子宫内膜金属蛋白酶的表达 用于区域特异性调节组织梯度。 Biol Reprod 59：1349-1359，1998.

This research aims to increase our understanding of the stromal-epithelial interactions that mediate the action of steroids in the reproductive tract. Our studies focus on the regulation and effects of specific growth factors, and on specific enzymes called matrix metalloproteinases (MMPs). Our studies have progressed in three main areas. First, we have characterized two novel forms of hepatocyte growth factor (HGF) expressed in the macaque endometrium. These two truncated transcripts of HGF are similar to two variants (HGF/NK1 and HGF/NK2 ) that are reported for the human genome. Northern blot of total RNA from microdissected, estradiol-treated endometrium showed that HGF/SF mRNA was expressed at 10 fold higher levels in the functionalis than in the basalis zone. In situ hybridization confirmed this expression gradient and showed that specific signal was confined to the subepithelial and perivascular stromal cells. Second, we immunocytochemically localized expr ession of two forms of vascular endothelial growth factor (VEGF) receptor, Type I (FLT1) and Type II (flk1/KDR) in the macaque endometrium. FLT1 staining was detected on the endothelial surface of small vessels and muscles of larger spiral arteries. Arterial staining was strongest in monkeys treated with estradiol plus progesterone (E2 + P), suggesting that VEGF may play a role during luteal phase artery growth. KDR staining was also evident in vascular endothelial cells. However, when P was withdrawn at the end of the cycle, a wave of strong KDR staining was observed in the stromal cells of the upper functionalis zone. KDR in stromal cells may play a functional role in remodeling the endometrium at the end of the menstrual cycle. Third, a critical period of P withdrawal is required to induce menstruation. We have evaluated expression of various matrix metalloproteinases (MMPs) during and after the critical period. When P is replaced during the critical period, expression of M MP-1, MMP-2, MMP-3, and TIMP 1 are blocked. However, when P is replaced after the critical period, some but not all MMPs are blocked. This indicates that MMPs vary both in their sensitivity to P suppression and their importance in menstruation. FUNDING NIH HD19182 PUBLICATIONS Lindsey JS, Brenner RM. Rhesus macaque endometrium expresses two novel transcripts of hepatocyte growth factor/scatter factor. Biol Reprod (Suppl 1) 58:173 (abstract 324). Lindsey JS, Slayden OD, Brenner RM. A zonal gradient of hepatocyte growth factor/scatter factor expression in rhesus macaque endometrium. Mol Biol Cell 9:477a,1998 (abstract). Rudolph-Owen LA, Slayden OD, Matrisian LM, Brenner RM. Matrix metalloproteinase expression in Macaca mulatta endometrium Evidence for zone-specific regulatory tissue gradients. Biol Reprod 59:1349-1359, 1998.