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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.

当哺乳大鼠注射多巴胺 (DA) 激动剂时产后 2-5 天服用溴隐亭，这基本上降低轻度患者的 PRL 浓度而不消除哺乳期，其后代表现出结节漏斗部 DA (TIDA) 系统和年轻时血清 PRL 升高成年人。此外，成人体内的细胞数量较多。新生 PRL 缺陷大鼠的垂体及其泌乳素细胞对 PRL 的反应性降低抑制 DA 的作用并增加对 PRL 的反应性 TRH 的刺激作用。这些影响 1) 不是由于非溴隐亭的具体作用，因为基本上无法检测到药物水平从母亲传递给新生儿牛奶; 2) 通过用溴隐亭替代 PRL 来预防接受治疗的母亲； 3) 如果溴隐亭是，则不会发生在产后第二周对母亲进行给药。这些发现提出了这样的假设：牛奶中的 PRL 新生儿影响 TIDA 神经元的生长和/或成熟以及垂体催乳素，以及里程缺乏在产后关键时期衍生的 PRL 可能具有长期 PRL 神经内分泌调节的持久影响分泌。本提案的具体目标是： 1) 建立功能发展的正常时间进程 TIDA 系统，使用 DA 浓度测量和合成率，并测试PRL和新生儿PRL的影响发展过程中的不足； 2）调查新生儿 PRL 缺乏对 TIDA 神经元数量的影响，使用免疫细胞化学检测酪氨酸羟化酶； 3）检查新生儿 PRL 缺乏是否会改变 TIDA 神经元的反应对其正常的调节影响，使用体内和体外方法； 4）调查新生儿PRL的后果成人对 PRL 合成和释放调节的缺陷刺激性或抑制性促垂体激素，或通过雌二醇，使用培养的垂体前叶细胞； 5）测试促生长激素的受体结合是否和/或它们与第二信使系统（例如腺苷酸）的偶联环化酶/cAMP，因新生儿 PRL 缺乏而永久改变； 6) 测试新生儿PRL缺乏是否影响数量和/或垂体催乳素细胞的形态，分泌 PRL 的形式以及 PRL 分泌的特点大鼠一生中的泌乳素细胞。