IONIC CHANNELS IN PITUITARY SOMATOTROPHS

脊椎动物出生后的生长主要是由生长调节的 生长激素(GH)由垂体前叶的促生长激素细胞释放。 这些细胞的GH分泌本身受下丘脑的控制 和外周多肽荷尔蒙。在许多分泌细胞中， 荷尔蒙分泌与细胞的电活动紧密相连 活性，最常见的是通过电压敏感的钙(钙) 频道。不带电的膜电流 促生长激素细胞的活性，以及这些通道的调节 具体的多肽激素还没有被研究。这 知识将是理解 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，将获得经鉴定的生长激素细胞。 用于在培养中使用不连续梯度 离心法或反向溶血空斑试验。这些细胞 将用标准细胞内电压和贴片电压进行研究 钳夹技术。研究的目的将是：1)描述 培养的大鼠垂体生长激素细胞的电学特性 并鉴定和表征下面的膜 电流：2)识别产生的离子电导变化 已知的三种多肽激素在促生长激素中的作用 调节体内生长激素的分泌。这些多肽包括生长 激素释放因子、生长抑素和胰岛素样物质 生长因子-I(IGF-I)；3)确定细胞内 CAMP、二酰甘油和GTP结合等信使 蛋白质调节生长激素细胞的通道活动，与之相关的是， 如果这些分子介导肽诱导的电导变化； 4)了解钙离子是否通过电压敏感通道进入 可以将电活动与荷尔蒙的合成结合起来 生长激素细胞和其他垂体腺细胞。 用于鉴定生长激素细胞并探索它们的技术 离子电流可以施加到其他类型的垂体细胞上， 据推测，到下丘脑的多肽分泌细胞， 它控制着脑下垂体前叶的激素释放。因此， 对这些生物物理机制的描述 中枢调节整个内分泌的功能 这个系统似乎是可行的。

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.