NEUROCHEMICAL CONTROL OF OXYTOCIN RELEASE

催产素释放的神经化学控制

• 批准号: 3317906
• 负责人: WILLIAM R CROWLEY
• 金额: $ 12.05万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3317906
• 关键词: adenylate cyclase; bromocriptine; cyclic AMP; dopamine; endocrine disorder; estradiol; high performance liquid chromatography; hormone receptor; hormone regulation /control mechanism; hyperprolactinemia; hypothalamus; immunocytochemistry; laboratory rat; lactation; median eminence; milk; neuroendocrine system; neurogenesis; neurons; newborn animals; nutrition related tag; prolactin; second messengers; thyrotropin releasing hormone; tissue /cell culture; tyrosine 3 monooxygenase

When lactating rats are injected with the dopamine (DA) agonist bromocriptine during days 2-5 postpartum, which substantially decreases the concentrations of PRL in milk 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 from neonatal PRL-deficient rats, and their lactotrophe cells show decreased responsiveness to the PRL-inhibiting effects of DA and increased 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 milk- 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 and 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; 30 to examine whether neonatal PRL deficiency alters the response of TIDA neurons to their normal regulatory influences, using iv 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.

给哺乳期大鼠注射多巴胺(DA)激动剂 溴隐亭在产后2-5天内，大大减少 在不取消哺乳的情况下，牛奶中催乳素的浓度，其 子代表现出漏斗状DA(TIDA)结节活性降低 系统和升高的血清催乳素作为年轻成年人。此外，在成体中， 催乳素缺乏症新生儿脑垂体腺细胞较多 大鼠和它们的促乳素细胞对 多巴胺对催乳素的抑制作用和对催乳素的反应性增强 DA的抑制作用和对PRL-的反应性增强- 促性腺激素释放激素的刺激作用。这些影响1)不是由于非特定原因造成的 溴隐亭的影响，因为基本上检测不到的水平 防止母亲通过母乳将药物传给新生儿；2)防止 通过将催乳素替代给溴隐亭治疗的母亲；以及3)不 如果在第二个月给母亲服用溴隐亭，就会发生 出生后一周。这些发现表明，从牛奶中提取的 新生儿PRL水平对TIDA生长和/或成熟的影响 神经细胞和脑下垂体催乳素，而牛奶的缺乏- 在出生后的关键时期衍生的催乳素可能会持续很长时间 催乳素分泌的神经内分泌调节的后果。具体的 本建议的目的是：1)建立正常的时间安排 对于TIDA系统的功能开发，使用以下测量 DA浓度和合成速率，并测试PRL和 新生儿催乳素缺乏在这个发展过程中：2) 新生儿催乳素缺乏对TIDA数量的影响 神经元，使用酪氨酸羟基酶的免疫细胞化学；30到 检查新生儿催乳素缺乏是否改变TIDA的反应 利用体内和体外实验研究神经元对其正常调节的影响 方法：4)调查新生儿催乳素缺乏的后果 刺激性激素对成体催乳素合成和释放的调节作用 抑制性促垂体激素，或由雌二醇，使用培养的 5)检测脑垂体前叶细胞的受体结合情况 促垂体激素和/或它们与第二信使的偶联 系统，如腺苷环化酶/cAMP，被永久性地改变 新生儿PRL缺乏症；6)检测新生儿PRL缺乏症 影响垂体促乳素细胞的数量和/或形态， 催乳素的分泌形式及其分泌特点 大鼠生命周期中的促乳素细胞。