HORMONAL CONTROL OF FEMALE REPRODUCTIVE TRACT

这项研究的目的是增加我们对 间质-上皮相互作用介导类固醇的作用 生殖道。我们的研究重点是监管和 特定生长因子的影响，以及对称为 基质金属蛋白酶(MMPs)。我们的研究取得了进展。 主要有三个方面。首先，我们描述了两种新形式的 肝细胞生长因子(HGF)在猕猴子宫内膜中表达。 这两个HGF的截短转录本类似于两个变体 (HGF/NK1和HGF/NK2)是已报道的人类基因组。 雌二醇处理的显微解剖总RNA的Northern杂交 子宫内膜HGF/SF m RNA表达增加10倍 功能区的水平高于基底区。就地 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，免疫细胞化学定位表达 在两种形式的血管内皮生长因子(VEGF)受体中， I型(Flt1)和II型(flk1/kdr)在猕猴子宫内膜中的表达。Flt1 在小血管内皮细胞表面检测到染色， 较大螺旋动脉的肌肉。动脉染色最强的是 用雌二醇加孕酮(E2+P)治疗的猴子，建议 提示血管内皮细胞生长因子可能在黄体期动脉发育过程中发挥作用。KDR 血管内皮细胞也有明显的染色。然而， 当周期结束时P被撤走，一波强劲的KDR 在上功能肌的间质细胞中观察到染色。 区域。基质细胞中的KDR可能在重塑中起功能作用 月经周期末期的子宫内膜。第三，一个关键的 需要停药一段时间才能引起月经。我们有 多种基质金属蛋白酶(MMPs)的表达 在关键时期期间和之后。在此期间更换P时 关键期、基质金属蛋白酶-1、基质金属蛋白酶-2、基质金属蛋白酶-3和基质金属蛋白酶1的表达 被封锁了。然而，当P在临界期之后被替换时，一些 但并不是所有的MMP都被屏蔽。这表明MMP在以下两个方面有所不同 它们对磷抑制的敏感性及其在体内的重要性 月经。资助NIH HD19182出版物Lindsey JS，Brenner Rm。恒河猴子宫内膜表达两个新的转录因子 肝细胞生长因子/分散因子。生物报告(附录1)58：173 (摘要324)。Lindsey JS，Slayden OD，Brenner RM。纬向坡度 肝细胞生长因子/分散因子在恒河猴中的表达 猕猴子宫内膜。Mol Biol Cell 9：477a，1998(摘要)。 Rudolph-Owen LA，Slayden OD，Matrisian LM，Brenner RM。矩阵 金属蛋白酶在猕猴子宫内膜中的表达 用于区域特定的调节组织梯度。生物报告 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.