NEURAL AND HORMONAL REGULATION OF LACTATION

哺乳期的神经和荷尔蒙调节

基本信息

批准号：
2194844
负责人：
CRAIG R BAUMRUCKER
金额：
$ 15.65万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-09-30 至 1995-07-31
项目状态：
已结题

项目摘要

When lactating rats are injected with the dopamine (DA) agonist bromocriptine during days 2-5 postpartum, which substantially decreases the concentrations of PRL in mild without abolishing lactation, their offspring exhibit decreased activity of the tuberoinfundibular DA (TIDA) system and elevated serum PRL as young adults. In addition, in the adult, there are more cells in the pituitary glands for neonatal PRL-deficient rats, and their lactotrophe cells show decreased responsiveness to the PRL- inhibiting effects of DA and increased responsiveness to the PRL- stimulating effects of TRH. These effects 1) are not due to non- specific effects of bromocriptine since essentially undetectable levels of the drug pass from the mother to the neonate via the milk; 2) are prevented by the replacement of PRL to bromocriptine treated mothers; and 3) do not occur if bromocriptine is administered to the mothers during the second postnatal week. These findings suggest the hypothesis that milk-derived PRL in the neonate influences the growth and/or maturation of TIDA neurons as well as pituitary lactotrophes, and that a deficiency in mile- derived PRL during a critical postnatal period may have long- lasting consequences for neuroendocrine regulation of PRL secretion. The specific aims of the present proposal are: 1) to establish the normal time course for the functional development of the TIDA system, using measurements of DA concentration and synthesis rate, and to test the effects of PRL ad of neonatal PRL deficiency on the course of this development; 2) to investigate the effects of neonatal PRL deficiency on the numbers of TIDA neurons, using immunocytochemistry for tyrosine hydroxylase; 3) to examine whether neonatal PRL deficiency alters the response of TIDA neurons to their normal regulatory influences, using in vivo and in vitro approaches; 4) to investigate the consequences of neonatal PRL deficiency on the adult regulation of PRL synthesis and release by stimulatory or inhibitory hypophyseotropic hormones, or by estradiol, using cultured anterior pituitary cells; 5) to test whether the receptor binding of hypophyseotropic hormones and/or their coupling to a second messenger system, such as adenylate cyclase/cAMP, are permanently altered by neonatal PRL deficiency; 6) to test whether neonatal PRL deficiency affects the numbers and/or morphology of pituitary lactotrophe cells, the secretory forms of PRL, and the characteristics of PRL secretion from lactotrophe cells over the lifespan of the rat.

当泌乳大鼠注入多巴胺（DA）激动剂时 2-5个产后2-5天的溴ircriptine 降低轻度prl的浓度而不会废除哺乳期，它们的后代表现出降低的活性结核病颌骨DA（TIDA）系统和升高的血清PRL年轻成年人。另外，在成年人中，有更多的细胞新生儿PRL缺陷大鼠的垂体及其乳酸营养细胞显示对PRL-的反应性降低抑制DA的影响和提高对PRL的反应能力 TRH的刺激效应。这些效果1）不是由于非溴张素的特定作用，因为本质上是无法检测的药物的水平通过母亲从母亲到新生儿牛奶; 2）通过将PRL替换为溴ircriptine阻止受到治疗的母亲； 3）如果溴张素是在第二个后周内给母亲管理。这些发现表明了以下假设新生儿会影响TIDA神经元的生长和/或成熟以及垂体乳腺营养不良，并且不足在关键的产后期间派生的PRL可能具有长期 PRL神经内分泌调节的持久后果分泌。本提案的具体目的是：1）建立正常的时间课程以进行功能发展 TIDA系统，使用DA浓度的测量和合成速率，并测试新生儿PRL的PRL AD的影响在这一发展过程中不足； 2）调查新生儿PRL缺乏对TIDA神经元数量的影响，使用免疫细胞化学用于酪氨酸羟化酶； 3）检查新生儿PRL缺乏是否会改变TIDA神经元的反应使用体内和体外的正常调节影响方法； 4）研究新生儿PRL的后果对成人调节PRL合成的不足，并通过刺激性或抑制性嗜性型激素，或雌二醇，使用培养的前垂体细胞； 5）测试降压激素和/或的受体结合是否它们连接到第二个信使系统，例如腺苷酸盐循环酶/cAMP被新生儿PRL缺乏症永久改变； 6）测试新生儿PRL缺乏症是否影响数字和/或垂体乳腺营养细胞的形态，分泌 PRL的形式以及PRL分泌的特征在大鼠的寿命上乳酸营养细胞。