NEUROENDOCRINE CONTROL OF ANTERIOR PITUITARY HORMONES

这是一项研究促垂体激素的调节和作用的建议。 生长激素(GH)和催乳素(PRL)的因子及其在 临床上的生长激素和催乳素分泌紊乱是一种延续 这个实验室的长期目标。身份识别和 人(异位)生长激素释放因子(GRF)的合成导致了 令人兴奋的调查新时代。GRF单独和联合作用的影响 与其他激素和代谢药物的关系将在注射后或 正常人和生长激素分泌障碍患者的输液 (肢端肥大症、神经性厌食症、糖尿病、特发性生长激素缺乏症)。这个 研究将定义正常人和正常人的生理控制机制 明确神经内分泌患者的病理生理机制 精神错乱。神经外GRF在中枢神经系统的分布 组织、肿瘤和血浆中GRF的测定 验证，将使用最近建立的 放射免疫分析。输注外源性GRF时的血浆测定 将用于评估新陈代谢清除率和分泌率 释放荷尔蒙。GRF在大鼠体内的生理调节 体外(下丘脑孵化)和体内(推拉)研究 套管)，使用RIA检测大鼠GRF。一个异源系统最初将是 在大鼠GRF可用之前一直使用。GRF和生长抑素的测定 (SRIF)将用于研究生长激素调控的整合 分泌，特别强调生长激素和生长激素的反馈作用 生长抑素-C、甲状腺激素、皮质酮、雌激素和潜能 神经肽能和-胺能递质。膜的作用 调节GRF和SRIF对生长激素细胞意志影响的受体 要下定决心。将尝试开发一种新的杂交瘤细胞系 人GRF分泌性肿瘤组织中GRF的细胞生物学研究 文化。循环中的多巴胺拮抗剂在多巴胺能中的作用 高催乳素血症状态下PRL分泌的调节将被研究 使用脑垂体细胞培养作为生物测定系统。一种实验模型 对于慢性肾功能衰竭的高催乳素血症将在 大鼠并用来识别异常的部位，负责 多巴胺抵抗及其相关机制。这些研究的结果 研究将提供更好的了解中枢神经系统在 临床上生长激素和催乳素分泌紊乱，并最终可能导致新的 治疗方法。

This is a proposal to study the regulation and actions of hypophysiotropic factors for growth hormone (GH) and prolactin (PRL) and their role in clinical disorders of GH and PRL secretion which represents a continuation of the long-standing goals of this laboratory. The identification and synthesis of human (ectopic) GH-releasing factor (GRF) has led to an exciting new era of investigation. Effects of GRF alone and in combination with other hormonal and metabolic agents will be studied after injection or infusion in normal subjects and in patients with disorders of GH secretion (acromegaly, anorexia nervosa, diabetes, idiopathic GH deficiency). The studies will define physiologic control mechanisms in the normals and identify pathophysiologic mechanisms in patients with neuroendocrine disorders. Distribution of GRF in the central nervous system, extraneural tissue, and tumors and measurement of GRF in plasma, after appropriate validation, will be performed using a recently established radioimmunoassay. Plasma measurements during infusion of exogenous GRF will be used for assessing metabolic clearance and secretion rates of the releasing hormone. Physiologic regulation of GRF in the rat will be studied in vitro (hypothalamic incubations) and in vivo (push-pull cannulae) using a RIA for rat GRF. A heterologous system will initially be used until rat GRF becomes available. Measurements of GRF and somatostatin (SRIF) will be used to study the integration of the regulation of GH secretion with particular emphasis on feedback effects of GH and somatomedin-C, thyroid hormone, corticosterone, estrogen, and potential neuropeptidergic and -aminergic transmitters. The role of membrane receptors in modulating the effects of GRF and SRIF on the somatotroph will be determined. An attempt will be made to develop a hybrid cell line of a human GRF-secreting tumor to study the cellular biology of GRF in tissue culture. The role of circulating dopamine antagonists in dopaminergic regulation of PRL secretion in hyperprolactinemic states will be studied using pituitary cell cultures as a bioassay system. An experimental model for the hyperprolactinemia of chronic renal failure will be developed in the rat and used to identify the site of the abnormality responsible for dopamine resistance and the mechanisms involved. The results of these studies will provide a better understanding of the role of the CNS in clinical disorders of GH and PRL secretion and may ultimately lead to new therapeutic approaches.