ESTROGEN MEDIATED PITUITARY TUMOR CELL GROWTH

这项研究的总体目标是确定 雌激素诱导的子宫、肾脏和垂体肿瘤来源的生长 大鼠垂体瘤细胞在体内和体内增殖的影响因素 体外培养。将在这些研究中使用的大鼠垂体瘤系是 GH3/C14和GH9C1细胞。我们对这些线路的研究表明， 雌激素是体内最佳生长所必需的，但不能 促进这些细胞在体外的持续生长。我们已经考虑过 对于文化中的这些观察，有几种可能的解释；然而， 我们最新的方法是问，是否有丝分裂的作用 体内雌激素可能是由类固醇激素调控的 生长因子的产生和分泌 荷尔蒙反应性垂体瘤细胞。为了评估一种可能的 雌激素诱导多肽生长因子的介导机制 第一次准备了从雌激素治疗和治疗中去除的组织的提取物 雌激素缺乏的动物，并通过添加 提取液在无血清培养液中培养至细胞。我们的实验证明 雌激素对GH3/C15垂体细胞生长因子水平的影响 在大鼠子宫和大鼠肾组织的提取物中。我们现在有了 从黄连冻干粉中提取纯化的垂体瘤细胞生长因子 羊的子宫和肾脏。这些活动是相关的，但不是完全相同的， Mr=4,200的多肽。这些属性现在进一步 调查。此外，自分泌/自分泌生长因子(MR 70,000) 已经在脑下垂体瘤中被发现。到目前为止，我们的实验表明 荷尔蒙反应性垂体瘤体内生长模型包括 一种涉及子宫、肾脏的机制，以及一种 肿瘤局部产生特定的多肽生长因子 雌激素反应性和自主性肿瘤。(D)

The overall objective of this research is to define the role of estrogen-induced uterine-, kidney-\and pituitary tumor-derived growth factors in the proliferation of rat pituitary tumor cells in vivo and in vitro. The rat pituitary tumor lines to be used in these studies are the GH3/C14 and GH9C1 cells. Our studies with these lines have shown that estrogens are required for optimal growth in vivo but are not capable of promoting continuous growth of these cells in vitro. We have considered several possible explanations for these observations in culture; however, our most recent approach has been to ask whether the mitogenic role of estrogens in vivo may be mediated by steroid hormone control of the production and secretion of growth factors specific for the hormone-responsive pituitary tumor cells. To evaluate the possibility of a mediated mechanism involving estrogen-induced polypeptide growth factor, we first prepared extracts of tissues removed from estrogen-treated and estrogen-deficient animals and assayed for growth activity by addition of extracts to cells in serum-free medium. Our experiments demonstrate that estrogens elevate the levels of growth factors for GH3/ C15 pituitary cells in extracts of both rat uterine and rat kidney tissue. We have now purified pituitary tumor cell growth factors from lyophilized powders of sheep uteri and kidneys. These activities are related, but not identical, polypeptides of Mr = 4,200. These properties are now under further investigation. In addition, autocrine/parocrine growth factor (Mr 70,000) have been identified in pituitary tumors. To date, our experiments suggest a model of hormone-responsive pituitary tumor growth in vivo that includes a mechanism that involves uterus, kidney, and an autocrime mechanism of tumors producing specific polypeptide growth factors locally within estrogenresponsive and autonomous tumors. (D)