NEURAL AND HORMONAL REGULATION OF LACTATION

哺乳期的神经和荷尔蒙调节

• 批准号: 3484931
• 负责人: CLARK GROSVENOR
• 金额: $ 22.09万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-30 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3484931
• 关键词: adenylate cyclase; adrenocorticotropic hormone; breast feeding; bromocriptine; cyclic AMP; dopamine; estrogens; forskolin; hormone inhibitor; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; lactation; median eminence; neural information processing; neuroendocrine system; nutrition related tag; oxytocin; parent offspring interaction; progesterone; prolactin; radioimmunoassay; second messengers; secretion; sympathetic nervous system; thyrotropin; thyrotropin releasing hormone; tissue /cell culture

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.

给哺乳期大鼠注射多巴胺(DA)激动剂 溴隐亭在产后2-5天，基本上 在不废除的情况下降低轻度催乳素的浓度 哺乳时，它们的后代表现出活性降低 青年期漏斗结节DA系统与血清催乳素升高 成年人。此外，在成体中， 新生催乳素缺乏大鼠的脑垂体腺 促乳素细胞对PRL-1的反应性降低 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 溴隐亭的特殊作用，因为基本上无法检测到 药物水平通过母体传递给新生儿 牛奶；2)通过将催乳素替换为溴隐亭来防止 接受治疗的母亲；3)如果溴隐亭 在产后第二周给母亲注射。 这些发现表明，假设乳源催乳素在 新生儿对TIDA神经元生长和/或成熟的影响 以及脑下乳汁营养素，这是里程的不足- 在关键的产后时期，衍生的催乳素可能会有很长的- 催乳素对神经内分泌调节的持久影响 分泌物。本建议的具体目标是：1) 建立正常的功能开发时间进程 TIDA系统，使用DA浓度和 合成率，并检测催乳素对新生儿催乳素的影响 在这一发展过程中的不足；2)调查 新生儿催乳素缺乏对TIDA神经元数量的影响 用免疫细胞化学法检测酪氨酸羟化酶；3)检测 新生儿催乳素缺乏是否改变TIDA神经元的反应 它们的正常调节作用，在体内和体外使用 方法：4)调查新生儿催乳素的后果 缺乏成体对催乳素合成和释放的调节 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 促垂体激素和/或 它们与第二信使系统的偶联，如腺苷 Cyclase/cAMP因新生儿PRL缺乏而永久改变； 6)测试新生儿催乳素缺乏是否会影响数量 和/或垂体促乳素细胞的形态，分泌物 催乳素的形式及其分泌的特点 大鼠生命周期中的促乳素细胞。