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STUDIES OF HEPATIC MAMMARY MITOGENIC FACTORS

肝乳腺有丝分裂因子的研究

基本信息

批准号：
3317697
负责人：
CHARLES S NICOLL
金额：
$ 9.11万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-04-01 至 1988-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3317697
关键词：
autoradiography breast neoplasms cellular oncology hormone biosynthesis hormone regulation /control mechanism insulinlike factor prolactin radioimmunoassay radiotracer tissue /cell culture tritium

项目摘要

We have obtained evidence that the growth-promoting action of prolactin (PRL) on the mucosal epithelium of the pigeon crop-sac involves synergism with an insulin-like growth factor (IGF). Furthermore, PRL stimulates the liver to secrete this synergistic activity, which we have called synlactin. Slices of liver from pregnant or lactating rats (but not from adult males or virgin females) secrete synlactin activity in vitro as measured by the crop-sac assay. Thus, the factor is secreted by the rat liver when the organ is influenced by high levels of placental lactogen (in pregancy) or pituitary PRL (lactation). The liver inculation medium samples that had synlactin activity in the crop-sac (from pregnant or lactating rats) also had mammary mitogenic activity in an assay involving explants of pregnant rat mammary glands. We propose to determine which cells in the mammary gland respond to the hepatic mammary mitogen. Mammary explants from virgin or pregnant rats will be incubated in liver incubation medium containing no synlactin activity (from male or virgin female liver) or with the activity (from pregnant or lactating liver). The mitogenic effect will be assessed by autoradiographic analysis of the incorporation of 3H-thymidine into cell nuclei. The effects of the liver incubation media will be compared with human IGF-I, PRL and insulin, and the effects of these hormones in different combinations will be determined. The proliferative effects of the hepatic factor and the other hormones (alone and in combination) will also be tested on rat mammary ductal and alveolar cells in a collagen gel matrix. The specificity of the hepatic mammary mitogenic effect will be evaluated by incubating explants of other tissue (salivary gland, kidney, thymus) in liver incubation medium with or without the activity. We will also investigate whether the liver participates in the regulation of mammary growth in vivo. This will be accomplished by infusing PRL and/or GH into the hepatic portal vein of virgin female rats using osmotic minipumps attached to PE-10 cannulae. This experiment should show whether PRL or GH can stimulate the liver to secrete factors that promote mammary ductal or lobulo-alveolar growth. Attempts will be made to purify and characterize the hepatic factor with synlactin activity from liver incubation medium, and to develop an RIA for it so that other aspects of its physiology can studied.

我们已经获得的证据表明，催乳素的促生长作用 (PRL)对鸽脐囊粘膜上皮的影响涉及协同作用胰岛素样生长因子（IGF）此外，PRL刺激肝脏分泌这种协同活性，我们称之为synlactin。妊娠或哺乳期大鼠（但非成年雄性）的肝脏切片或处女女性）在体外分泌催乳素活性，作物囊测定因此，该因子是由大鼠肝脏分泌时，器官受到高水平的胎盘催乳素的影响（妊娠），或垂体PRL（泌乳）。肝脏接种培养基样本，在作物囊（来自妊娠或哺乳期大鼠）中的合成乳素活性也在涉及妊娠的外植体的测定中具有乳腺有丝分裂活性大鼠乳腺。我们建议确定哪些细胞在乳腺反应，肝乳腺有丝分裂原未交配或妊娠大鼠的乳房外植体将在不含合成乳素的肝脏孵育培养基中孵育活性（来自雄性或处女雌性肝脏）或与活性（来自妊娠或哺乳期肝脏）。促有丝分裂作用将通过以下方式进行评估： ~ 3 H-胸苷掺入细胞的放射自显影分析原子核。将比较肝脏孵育培养基的效果，人IGF-I、PRL和胰岛素，以及这些激素在将确定不同的组合。的增殖效应肝因子和其它激素（单独和组合）将也可以在胶原凝胶中的大鼠乳腺导管和肺泡细胞上进行测试矩阵肝乳腺促有丝分裂作用的特异性将是通过孵育其它组织（唾液腺，肾，胸腺）在肝孵育培养基中具有或不具有活性。我们还将调查肝脏是否参与调节乳腺的生长。这将通过注入PRL来实现和/或GH进入处女雌性大鼠的肝门静脉，使用渗透压连接到PE-10插管的微型泵。这个实验可以证明 PRL或GH可以刺激肝脏分泌促进乳腺生长的因子，导管或小叶-肺泡生长。将尝试纯化和表征肝因子，从肝孵育培养基中提取合成乳素活性，并开发RIA，这样就可以研究它的其他生理学方面。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biological and immunological characterization of cleaved and 16K forms of rat prolactin.

DOI：
10.1210/endo-122-6-2892
发表时间：
1988-06
期刊：
Endocrinology
影响因子：
4.8
作者：
C. Clapp;P. Sears;D. Russell;J. Richards;Brett K. Lev Ay-Young;C. S. Nicoll
通讯作者：
C. Clapp;P. Sears;D. Russell;J. Richards;Brett K. Lev Ay-Young;C. S. Nicoll

Pigeon crop-sac as a model system for studying the direct and indirect effects of hormones and growth factors on cell growth and differentiation in vivo.

鸽嗉囊作为研究激素和生长因子对体内细胞生长和分化的直接和间接影响的模型系统。