Strategies for Analyzing the Processing of Proopiomelanocortin

罗伯特·多雷斯 脑下垂体是合成几种多肽激素的场所，这些多肽激素用作化学信使以影响多种功能，例如生长、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（称为激素原）是生物学上无活性的，必须通过酶进行各种加工步骤才能将无功能的激素原转化为生物学上有活性的激素。 这些重要的激素原之一是在中间垂体中发现的阿黑皮素原（POMC）。 POMC是促肾上腺皮质激素、促黑素细胞激素和内源性阿片样物质β-内啡肽的共同激素原。 POMC合成后，它经历了许多加工步骤，使这些活性激素。 细胞内发生酶促反应的位点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动物海蟾蜍的促黑素细胞中研究参与加工的两种重要酶（激素原转化酶1和2）的亚细胞协调以及发生这种加工的细胞内位置的提议。 由于垂体激素的适当合成对所有脊椎动物的生存至关重要，这些研究对于提供垂体细胞细胞生物学的新见解至关重要。

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.