NEURAL AND HORMONAL REGULATION OF LACTATION

哺乳期的神经和荷尔蒙调节

• 批准号: 3484926
• 负责人: CLARK GROSVENOR
• 金额: $ 19.81万
• 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/3484926
• 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.

当哺乳期大鼠注射多巴胺（DA）激动剂时， 在产后2-5天期间使用溴隐亭， 降低轻度泌乳素的浓度， 哺乳期，它们的后代表现出大脑活动的减少 结节漏斗DA（TIDA）系统和血清PRL升高 成年人了 此外，在成年人中，有更多的细胞在 垂体腺的新生PRL缺乏大鼠，和他们的 催乳细胞对PRL的反应性降低， DA的抑制作用和对PRL的反应性增加- TRH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 药物水平从母亲通过 牛奶; 2）通过将PRL替换为溴隐亭来预防 治疗的母亲;和3）如果溴隐亭是 在产后第二周期间给予母亲。 这些发现提示了一种假说，即在哺乳动物中， 新生儿影响TIDA神经元的生长和/或成熟， 以及垂体催乳素，而缺乏英里- 在出生后的关键时期获得的PRL可能具有长- PRL神经内分泌调节的持久后果 分泌物 本建议的具体目标是：1） 建立正常的时间进程的功能发展， TIDA系统，使用DA浓度的测量， 合成率，并检测催乳素和新生儿催乳素的作用 这一发展过程中的不足之处; 2）调查 新生儿PRL缺乏对TIDA神经元数量的影响， 酪氨酸羟化酶免疫细胞化学法; 3） 新生儿PRL缺乏是否会改变TIDA神经元的反应 在体内和体外， 方法; 4）调查新生儿PRL的后果 缺乏对PRL合成和释放的成人调节， 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 是否促垂体激素和/或 它们与第二信使系统如腺苷酸的偶联 环化酶/cAMP，被新生儿PRL缺乏永久改变; 6)以测试新生儿PRL缺乏是否会影响 和/或垂体催乳细胞的形态，分泌 催乳素的形式，以及催乳素分泌的特点， 在大鼠的整个生命周期中，