IONIC CHANNELS IN PITUITARY SOMATOTROPHS

脊椎动物出生后的生长主要受生长调节 由垂体前叶的生长激素细胞释放的激素（GH）。 这些细胞的GH分泌本身由下丘脑控制， 和外周肽激素。 在许多分泌细胞中， 激素的分泌与细胞的电流紧密相连， 活性，最常通过电压敏感性钙（Ca 2+） 渠道 膜电流， 生长激素细胞的活动，以及这些通道的调制， 还没有研究具体的肽激素。 这 知识将是必不可少的理解 调节生长激素分泌和生长的生理机制 在脊椎动物中。 在拟议的研究中，将获得已鉴定的生长激素细胞 对于使用不连续梯度或 离心或反向溶血空斑测定。 这些细胞 将使用标准细胞内电压和贴片电压进行研究 钳位技术 本研究的目的是：1）描述 培养的大鼠垂体生长激素细胞的电特性 并识别和表征底层膜 电流：2）确定产生的离子电导变化 在生长激素细胞中， 调节体内GH分泌。 这些肽包括生长 激素释放因子（GRF）、生长抑素和胰岛素样 生长因子-I（IGF-I）; 3）确定细胞内 信使如cAMP、甘油二酯和GTP结合 蛋白质调节生长激素细胞中的通道活性，相关地， 如果这些分子介导肽诱导的电导变化; 4)以确定钙离子是否通过电压敏感通道进入 可以将电活动与激素合成结合起来， 生长激素细胞和其他垂体细胞。 用于鉴定生长激素细胞并探索其 离子电流可以应用于其它垂体细胞类型， 据推测，下丘脑的肽分泌细胞， 控制垂体前叶激素的释放 因此，在本发明中， 生物物理机制的描述，这些 中心元素调节整个内分泌系统的功能 系统似乎可行。

Postnatal growth in vertebrates is primarily regulated by growth hormone (GH) released by somatotrophs of the anterior pituitary. GH secretion by these cells is itself controlled by hypothalamic and peripheral peptide hormones. In many secretory cells, hormone secretion is tightly coupled to the cell's electrical activity, most often through voltage-sensitive calcium (Ca2+) channels. The membrane currents which underly electrical activity in somatotrophs, and the modulation of these channels by the specific peptide hormones have not been studied. This knowledge will be essential for an understanding of the physiological mechanisms which regulate GH secretion and growth in vertebrates. In the proposed studies, identified somatotrophs will be obtained for study in culture using either discontinuous gradient centrifugation or the reverse hemolytic plaque assay. These cells will be studied with standard intracellular and patch voltage clamp techniques. The aims of the study will be: 1) to describe the electrical properties of cultured rat pituitary somatotrophs and to identify and characterize the underlying membrane currents: 2) to identify the ionic conductance changes produced in somatotrophs by the three peptide hormones which are known to regulate GH secretion in vivo. These peptides include growth hormone releasing factor (GRF), somastatin, and insulin-like growth factor-I (IGF-I); 3) to determine whether intracellular messengers such as cAMP, diacylglycerol, and GTP-binding proteins regulate channel activity in somatotrophs and, relatedly, if these molecules mediate peptide-induced conductance changes; 4) to find whether Ca2+ entry through voltage-sensitive channels can couple electrical activity to hormone synthesis in somatotrophs and other pituitary cells. The techniques used to identify somatotrophs and explore their ionic currents can be applied to other pituitary cells types and, presumably, to the peptide secreting cells of the hypothalamus, which control hormone release from the anterior pituitary. Thus, a description of the biophysical mechanisms by which these central elements reulate the function of the entire endocrine system seems feasible.