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FUNCTIONAL SIGNIFICANCE OF 16K PROLACTIN

16K 催乳素的功能意义

基本信息

批准号：
3238451
负责人：
CHARLES S NICOLL
金额：
$ 8.55万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1991-03-31
项目状态：
已结题

项目摘要

Prolactin (PRL) stimulates the growth and function of target tissues such as the mammary gland (MG) and the prostate and may contribute to the development of breast and prostate cancer. However, no clear correlation has been found between circulating PRL levels (measured by radioimmunoassay; RIA) and the incidence and risk of mammary tumors in women. Such lack of correlation could be explained by the existence of bioactive forms of PRL with low immunoactivity. We have isolated a 16K fragment of PRL, generated in vitro by the MG, with a high bioassay: RIA ratio. Using a specific RIA for 16K PRL that we have developed, we have found that significant amounts of 16K PRL are present in the circulation of rats in different physiological states. Knowledge about the functional relevance of the proteolysis of PRL into the 16K fragment by the MG may add to the understanding of the role of PRL in the regulation of normal and cancerous mammary growth. To analyze whether 16K plays a role in MG function, we will: A. Test if for lactogenic activity by measuring casein synthesis by rat mammary cells. B. Determine which tissues can produce cleaved and 16K PRL in vitro and whether the rate of production varies with the physiological state of the animal. C. Survey various tissues for the presence of specific receptors for the 16K PRL to obtain information on potential target organs of the fragment. D. Determine whether 16K in serum is monomeric, aggregated or carrier bound. E. Measure by RIA the 16K levels in tissues (pituitary, liver and MG) and serum of rats whose MG are in different physiological states of growth and function, and in rats bearing chemically- induced (DMBA) mammary tumors. 16K PRL may also be produced inside the stomach of rat pups from the PRL in milk. We found that enzymes required for the proteolysis of PRL into the 16K fragment are present in milk, and dependent on an acid pH. To study whether 16K PRL is present and exerts some effect in the nursing young, we will: A. Determine the 16K levels in stomach milk and in the circulation of suckling rats. B. Analyze the effect of passive immunization against 16K PRL on the rate of growth of infant rats. C. Determine whether specific 16K receptors are present in various tissues of rat pups.

催乳素（PRL）刺激靶细胞的生长和功能组织如乳腺（MG）和前列腺，并且可以会导致乳腺癌和前列腺癌。然而，没有发现循环之间的明确相关性。 PRL水平（通过放射免疫测定法测量; RIA）和女性乳腺肿瘤的发病率和风险。这种缺乏相关性可以解释为存在生物活性形式低免疫活性的PRL。我们分离出了一个16 K 片段的PRL，在体外产生的MG，具有高生物测定：RIA比值。使用特定的RIA检测16 K PRL，我们发现，大量的16 K 催乳素存在于大鼠的循环中，生理状态。关于功能相关性的知识 MG将PRL蛋白水解成16 K片段可能增加了了解PRL在调节正常和癌变的乳房生长。分析16 K是否在MG功能中发挥作用，我们将： A. 通过测量酪蛋白合成来检测催乳活性通过大鼠乳腺细胞。 B。确定哪些组织可以产生切割和16 K PRL，体外，以及生产率是否随动物的生理状态。 C. 检查各种组织是否存在特定受体用于16 K PRL，以获得潜在靶器官的信息的碎片。 D. 确定血清中的16 K是单体的、聚集的还是运营商绑定。 E. 放射免疫法测定垂体、肝、 MG）和血清中MG处于不同生理状态的大鼠生长和功能的状态，以及在大鼠携带化学- DMBA诱导的乳腺肿瘤。 16 K PRL也可在幼鼠胃内产生从牛奶中的催乳素我们发现，将PRL蛋白水解成16 K片段存在于牛奶中，为了研究是否存在16 K PRL，并在哺乳期青年中发挥一定的作用，我们将： A. 测定胃乳和胃粘膜中的16 K水平乳鼠的血液循环。 B。 16 K催乳素被动免疫效果分析对幼鼠生长速度的影响。 C. 确定是否存在特定的16 K受体，幼鼠的各种组织。