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，促肾上腺皮质激素（POMC）。该前体不仅含有ACTH序列，还含有-促黑素、-促黑素和内源性阿片肽-内啡肽的序列。POMC在垂体的两个区域以及中枢神经系统中不同的神经元组中合成。尽管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。对这个问题的见解可以从对物种的研究中获得，这些物种似乎表现出可以被认为是祖先的特征。这项研究将集中在两个“主要物种”上，即全颌鱼（Amia calva）和澳大利亚肺鱼（Neoceratodus forsteri）。这些物种在硬骨鱼的系统发育中占有举足轻重的地位。全骨鱼在进化过程中产生了硬骨鱼，现代硬骨鱼，肺鱼在进化过程中产生了四足动物。本项目将重点研究这些物种的POMC终产物的生物化学。这些研究将为促阿皮质素生物合成途径的进化提供新的信息，并将进一步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.