PERINATAL MATURATION OF PITUITARY GROWTH HORMONE RELEASE

这项研究建议关注的是 垂体腺功能可能是生长激素的决定因素 (GH)在发育期大鼠体内释放。 调节幼年动物生长激素分泌的因素有 我不明白。PI和其他人的活体研究表明 间接地，脑下垂体可能会有成熟的变化 对生长激素释放的生理调节的反应性。按顺序 为了直接评估这个问题，当前的提案审查了 体外培养的发育大鼠垂体细胞释放GH。老鼠 将在关键发展阶段进行研究，这些阶段与 循环生长激素水平的主要变化：胎儿(20d 孕期)、出生后第2天和第15天，以及成年(3-4个月)。这个 项目将决定1)开发的相对敏感度 生长激素释放因子(GHRF)，2) 生长抑素(SRIF)抑制生长激素的相对有效性 在早期发育过程中释放，3)易感性 幼龄垂体腺对持续性脱敏的影响 暴露于GHRF和生长抑素，4)对 前列腺素E_1和E_2(PGE_1、PGE_2)对生长激素释放的影响 早期发育及其与GHRF的相互作用，5) 胰岛素样物质负反馈效应的研究进展 生长因子对垂体生长激素释放的影响。初步结果 表明GHRF和SRIF的影响具有明显的年龄相关性 在生长激素释放时。为了进一步定义潜在的机制 这些垂体功能的发育性变化，也是 计划确定未成熟者的相对能力 脑下垂体对GHRF和7)产生cAMP的反应 发育中的促生长激素细胞对生长激素的相对敏感性 增加细胞内cAMP含量的分泌物 不依赖于GHRF受体。初步结果显示 生长激素释放的个体数量差异 (Bu)2cAMP和forskolin，暗示有可能 CAMP远端促生长激素功能的成熟性变化 队形。 长期目标是确定哪些因素有助于 正常神经内分泌对生长激素分泌调控的成熟 为了了解生长激素的两个生理决定因素 生长激素在生长动物体内的释放及其病理生理学 分泌障碍。垂体腺功能的成熟变化 具有潜在的重要性，因为A)可能是 血浆生长激素水平的发育变化，B)一个概念 神经内分泌个体发生，以及C)可能的功能障碍部位 这可能与生长激素的神经分泌障碍有关。 童年。

This research proposal focuses on maturational changes in pituitary function as a possible determinant of growth hormone (GH) release in the developing rat. The factors which regualte GH secretion in immature animals are not understood. In vivo studies by the PI and others suggest indirectly that there may be maturational changes in pituitary responisiveness to physiologic regulators of GH release. In order to directly evaluate this question, the current proposal examines GH release from cultured pituitary cells of developing rats. Rats will be studied at key developmental stages which coincide with major changes in circulating GH levels: fetus (day 20 of gestation), postnatal days 2 and 15, and adults (3-4 mo). The project will determine 1) the relative sensitivity of the developing somatotroph to growth hormone-releasing factor (GHRF), 2) the relative effectiveness of somatostatin (SRIF) in inhibiting GH release during early development, 3) the susceptibility of the immature pituitary to the desensitizing effectis of continuous exposure to GHRF and somatostatin, 4) the influence of prostaglandins E1 and E2 (PGE1, PGE2) on GH release during early development and their interaction with GHRF, 5) the development of the negative feedback effect of Insulin-like Growth Factors on pituitary GH release. Preliminary results indicate marked age-dependency in the effects of GHRF and SRIF on GH release. To further define the mechanisms underlying these developmental alterations in pituitary function, it is also planned to determine 6) the relative capacity of the immature pituitary to generate cAMP in response to GHRF and 7) the relative sensitivity of the developing somatotroph to GH secretogogues which increase intracellular cAMP content independent of the GHRF receptor. Preliminary results indicate quantitative ontogenic differences in the release of GH by (Bu)2cAMP and forskolin, suggesting the possibility of maturational changes in somatotroph function distal to cAMP formation. The long term goal is to identify those factors which contribute to the maturation of normal neuroendocrine control of GH secretion in order to understand both physiologic determinants of GH release in growing animals and the pathophysiology of GH secretory disorders. Maturational changes in pituitary function are of potential importance as A) a possible explanation for developmental changes in plasma GH levels, B) a concept in neuroendocrine ontogeny, and C) a possible site of dysfunction which may contribute to neurosecretory disorders of GH in childhood.