Strategies for Analyzing the Processing of Proopiomelanocortin

IBN-9412115罗伯特·多雷斯脑下垂体是几种多肽激素的合成场所，这些激素被用作化学信使，影响各种功能，如生长、生殖和慢性应激调节。多肽激素的一个特征是，首先在细胞内合成的分子(称为前激素)在生物上是不活跃的，必须经过各种酶处理步骤才能将不起作用的前激素转化为具有生物活性的激素。其中一种重要的前激素是发现于中间垂体腺的前阿片黑素皮质素(POMC)。POMC是促肾上腺皮质激素、黑素细胞刺激素和内源性阿片类药物β-内啡肽的常见前体激素。在POMC合成后，它经历了一系列的加工步骤来制造这些活性激素。人们对细胞内发生酶反应的部位以及所涉及的酶的调节和性质知之甚少。这是一项在无尾两栖类--中华大蟾蜍的嗜黑细胞中研究参与加工的两种重要酶(前激素转换酶1和2)的亚细胞协调以及细胞内发生这一加工的位置的建议。由于脑下垂体激素的适当合成对所有脊椎动物的生存至关重要，因此这些研究对于为脑下垂体细胞的细胞生物学提供新的见解至关重要。

IBN-9412115 Robert Dores The pituitary gland is the site for synthesis of several polypeptide hormones which are used as chemical messenger to influence a variety of functions such as growth, reproduction, and chronic stress regulation. One characteristic of polypeptide hormones is that the molecule that is first synthesized inside the cell (called a prohormone) is biologically inactive and must undergo a variety of processing steps by enzymes to convert the non-functional prohormone into a biologically active hormone. One of these important prohormones is proopiomelanocortin (POMC) found in the intermediate pituitary. POMC is the common prohormone for adrenocorticotropin, melanocyte-stimulating hormone, and the endogenous opioid, beta-endorphin. After POMC is synthesized, it undergoes a number of processing steps to make these active hormones. The sites inside the cell where the enzymatic reactions take place and the regulation and nature of the enzymes involved are poorly understood. This is a proposal to study in melanotropic cells of the anuran amphibian, Bufo marinus, the subcellular coordination of two important enzymes (prohormone convertase 1 and 2) that are involved in the processing and the location inside the cell where this processing occurs. Since the proper synthesis of pituitary hormones is essential to the survival of all vertebrates, these studies are critical for providing new insights into the cell biology of pituitary cells.