NEUROCHEMICAL CONTROL OF OXYTOCIN RELEASE

催产素释放的神经化学控制

• 批准号: 3317907
• 负责人: WILLIAM R CROWLEY
• 金额: $ 12.63万
• 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/3317907
• 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