Analysis of Holostean Pituitary Pro-opiomelanocortin Systems

垂体激素促肾上腺皮质激素(ACTH)来源于前体蛋白前阿片黑素皮质素(POMC)。该前体不仅含有ACTH序列，还含有α-促黑素激素、β-促黑激素和内源性阿片肽β-内啡肽的序列。POMC在脑下垂体的两个区域以及中枢神经系统的不同神经元中合成。虽然这种生物合成途径存在于所有现存的脊椎动物中，但很少有研究试图解释这种生物合成途径是如何进化的。这个问题的洞察力可以从对似乎表现出可以被认为是祖先的特征的物种的研究中获得。这项研究将集中在两个“主线物种”，海龙鱼，Amia Calva，和澳大利亚肺鱼，新角鱼forsteri。这些物种在硬骨鱼的系统发育中占有举足轻重的地位。海龙鱼的进化路线产生了硬骨鱼，现代的硬骨鱼和肺潮鱼的进化路线产生了四足动物。本提案中的项目将侧重于这些物种中POMC最终产物的生物化学。这些研究将为前阿片黑素皮质素生物合成途径的进化提供新的信息，并将加深我们对内分泌细胞产生化学信号的机制的理解。

The pituitary hormone, adrenocorticotropin (ACTH), is derived from the precursor protein, pro-opiomelanocortin (POMC). This precursor not only contains the sequence of ACTH, but also the sequences of alpha-melanotropin, beta-melanotropin and the endogenous opiod peptide, beta-endorphin. POMC is synthesized in two regions of the pituitary as well as in distinct sets of neurons in the central nervous system. Although this biosynthetic pathway is present in all extant vertebrates, few studies have attempted to explain how this biosynthetic pathway evoluted. Insights into this issue can be obtained from studies on species that appear to exhibit traits that can be considered ancestral. This study will focus on two "mainline species," the holostean fish, Amia calva, and the Australian lungfish, Neoceratodus forsteri. These species occupy pivotal positions in the phylogeny of the bony fish. The holostean fish are on a line of evolution which gave rise to the teleosts, the modern bony fish, and the lungfush are on the line of evolution which gave rise to the tetrapods. The projects in this proposal will focus on the biochemistry of the POMC end products in these species. These studies will provide new information on the evolution of the pro-opiomelanocortin biosynthetic pathway and will further our understanding of the mechanisms involved in production of chemical signals by endocrine cells.