NEUROENDOCRINE CONTROL OF ANTERIOR PITUITARY HORMONES

垂体前叶激素的神经内分泌控制

• 批准号: 3152101
• 负责人: LAWRENCE A FROHMAN
• 金额: $ 25.25万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152101
• 关键词: acromegaly; alpha methyldopamine; blood chemistry; catecholamine inhibitor; dopamine; endocrine disorder; endocrine pharmacology; estrogens; hormone regulation /control mechanism; human subject; hyperprolactinemia; neural information processing; neuroendocrine system; orphan disease /drug; peptide hormone metabolism; pituitary disorders; pituitary hormones; pituitary neoplasms; prolactin; prolactin releasing /inhibiting factor; radioimmunoassay; somatostatin; somatotropin; thyroid hormones; tissue /cell culture

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.

这是一个研究垂体促性腺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 GH和PRL分泌的临床疾病， 这个实验室的长期目标。 确定和 人（异位）GH-释放因子（GRF）的合成导致了 激动人心的调查新时代 GRF单独和联合使用的效果 将在注射后研究与其他激素和代谢药物的联合使用，或 在正常受试者和GH分泌障碍患者中输注 （肢端肥大症、神经性厌食症、糖尿病、特发性GH缺乏症）。 的 研究将确定正常人的生理控制机制， 确定神经内分泌疾病患者病理生理机制 紊乱 GRF在中枢神经系统中的分布 组织和肿瘤中的GRF和血浆中的GRF的测量，在适当的 验证，将使用最近建立的 放射免疫法 外源性GRF输注期间的血浆测量 将用于评估代谢清除率和分泌率， 释放荷尔蒙 GRF在大鼠中的生理调节将是 体外（下丘脑孵育）和体内（推拉）研究 插管）使用RIA测定大鼠GRF。 异源系统最初将 使用直至大鼠GRF可用。 GRF和生长抑素的测量 （SRIF）将用于研究GH调节的整合 特别强调GH的反馈作用， 生长调节素C、甲状腺激素、皮质酮、雌激素和潜在 神经肽能和β-胺能递质。 膜的作用 受体在调节GRF和SRIF对生长激素的作用中的作用， 被确定。 将尝试开发一种杂交细胞系， 人GRF分泌性肿瘤，以研究组织中GRF的细胞生物学 文化 循环多巴胺受体拮抗剂在多巴胺能神经系统中的作用 将研究高催乳素血症状态下PRL分泌的调节 使用垂体细胞培养物作为生物测定系统。 实验模型 慢性肾功能衰竭的高泌乳素血症将在 大鼠，并用于确定负责异常的部位， 多巴胺抵抗及其机制。 的结果予以 研究将提供更好的了解中枢神经系统的作用， GH和PRL分泌的临床疾病，并可能最终导致新的 治疗方法。

项目成果

Secretagogues and the somatotrope: signaling and proliferation.

• 发表时间: 2000-12
• 期刊: Recent progress in hormone research
• 作者: L. Frohman;R. Kineman;J. Kamegai;S. Park;L. T. Teixeira;K. T. Coschigano;J. J. Kopchic-J.

Effects of growth hormone-releasing factor on growth hormone secretion in acromegaly.

生长激素释放因子对肢端肥大症生长激素分泌的影响。

• DOI: 10.1210/jcem-60-2-251
• 发表时间: 1985
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Gelato,MC;Merriam,GR;Vance,ML;Goldman,JA;Webb,C;Evans,WS;Rock,J;Oldfield,EH;Molitch,ME;Rivier,J
• 通讯作者: Rivier,J

Diethylstilbestrol inhibits tumor growth and prolactin production in rat pituitary tumors.

己烯雌酚抑制大鼠垂体瘤的肿瘤生长和催乳素的产生。

• 发表时间: 1985
• 期刊: The American journal of pathology
• 作者: Lloyd,RV;Landefeld,TD;Maslar,I;Frohman,LA
• 通讯作者: Frohman,LA

Acromegaly due to secretion of growth hormone by an ectopic pancreatic islet-cell tumor.

由于异位胰岛细胞肿瘤分泌生长激素而导致肢端肥大症。

• DOI: 10.1056/nejm198501033120103
• 发表时间: 1985
• 期刊: The New England journal of medicine
• 作者: Melmed,S;Ezrin,C;Kovacs,K;Goodman,RS;Frohman,LA
• 通讯作者: Frohman,LA

Ectopic growth hormone-releasing factor and dibutyryl cyclic adenosine monophosphate-stimulated growth hormone release in vitro: effects of corticosterone and estradiol.

异位生长激素释放因子和二丁酰环单磷酸腺苷刺激的体外生长激素释放：皮质酮和雌二醇的作用。

• DOI: 10.1210/endo-113-4-1191
• 发表时间: 1983
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Webb,CB;Szabo,M;Frohman,LA
• 通讯作者: Frohman,LA