ANDROGEN INHIBITION OF FETAL LUNG MATURATION

该项目的主要目标是更好地界定 控制胎儿肺的成熟。 这将通过 继续研究性别差异的机制， 胎儿肺发育，解决四个具体目标。 具体目标不。 1是进一步表征调节生产的机制， 成纤维细胞肺细胞因子（FPF）的胎儿肺成纤维细胞。 鼠标 将使用睾丸雌性化模型（Tfm小鼠）。 将研究 FPF表达的性别差异机制， 和雄激素不敏感的男性胎儿，通过确定是否激素或 外源性生长因子如表皮生长因子（EGF）， 血小板衍生生长因子（PDGF）或生长调节素C刺激 生产FPF。 第二个具体目标是研究由下列因素产生的因素： 胎肺调节其生长和分化。 的存在 不同发育阶段的不同因素， 调节生长和分化是一个可能的解释， 在表面活性剂合成中出现差异。 FPF条件培养基， 将对Tfm小鼠进行研究，以确定在Tfm小鼠中缺乏FPF活性是否是一个重要的因素。 男性与促进生长的活动相吻合。 性别特异性器官培养 胎兔肺将用于进一步的实验， 来自胎肺成熟早期和晚期的条件培养基。 将测试该条件培养基的生长促进和 在男性和女性的分化活动。 具体目标3是 研究内源性生长因子表达的调控机制 肺部的因素。 激素对内源性激素的调节作用 或外源性生长因子（EGF、PDGF、生长调节素-C）。 具体目标4是开始描述增长的特征， 分化因子由胎儿肺所确定的特异性 目标二。 将通过HPLC和凝胶柱对条件培养基进行分馏 以分离活性级分。 将开展研究， 并开始对其进行表征。 的 从这些研究中获得的信息将有助于制定 早产儿肺透明膜病的预防策略 等 战略必须坚定地建立在对胎儿肺事件的了解的基础上， 需要在男性和女性中加强的发展。 此外 这些研究将为我们提供有价值的见解， 生物钟控制着发育的时间

The main objective of this project is to better define the mechanisms controlling maturation of the fetal lung. This will be accomplished by continuing the study of the mechanisms of the sex difference in the timing of fetal lung development, addressing four specific aims. Specific Aim No. 1 is to further characterize the mechanism regulating the production of fibroblast pneumonocyte factor (FPF) by fetal lung fibroblasts. The mouse model of testicular feminization (Tfm mouse) will be used. Will study the mechanism of the sex difference in the expression of FPF in male, female, and androgen-insensitive male fetuses, by determining whether hormones or exogenous growth factors such as epidermal growth factor (EGF), platlet-derived growth factor (PDGF) or somatomedin C stimulate the production of FPF. Specific Aim No. 2 is to study the factors produced by the fetal lung to regulate its growth and differentiation. The presence of different factors at different developmental stages which sequentially regulate growth and differentiation is a likely explanation of how sex differences in surfactant synthesis arise. FPF conditioned media from the Tfm mouse will be studied to identify whether the lack of FPF activity in males coincides with growth-promoting activity. Sex-specific organ culture of fetal rabbit lung will be used in further experiments to prepare conditioned media from early and late stages in fetal lung maturation. This conditioned media will be tested for growth-promoting and differentiation activity in males and females. Specific Aim No. 3 is to study the mechanisms which regulate the expression of endogenous growth factors in the lung. The hormonal mediation of the effects of endogenous or exogenous growth factors (EGF, PDGF, somatomedin-C) will be studied. Specific Aim No. 4 is to begin to characterize the growth and differentiation factors made by the fetal lung as identified in Specific Aim No. 2. Conditioned media will be fractionated by HPLC and gel columns to isolate the active fractions. Studies will be initiated to isolate the specific proteins involved and to begin to characterize them. The information gained from these studies will be useful for devising strategies to prevent hyaline membrane disease in premature infants. Such strategies must be firmly based on a knowledge of the events in fetal lung development which need to be enhanced in male and in females. In addition these studies will provide valuable insights into the general understanding of the biological clock which regulates the timing of developmental events.