Bicknell A B, Savva D, Lowry P J
School of Animal and Microbial Sciences, University of Reading, Berkshire.
Endocr Res. 1996 Nov;22(4):385-93. doi: 10.1080/07435809609043722.
Pro-opiomelanocortin (POMC) is a polyhormone precursor produced predominantly in the pars distalis and pars intermedia of the pituitary gland where it undergoes tissue specific processing to produce a whole array of peptides. We have shown previously that peptides derived from the N-terminal region of POMC are involved in adrenal growth in rats. Using specific two site immunoradiometric assays we have found that the plasma of 17 week old fetal sheep contain a 50 fold excess of pro-gamma-MSH over ACTH. As term approached, the levels of pro-gamma-MSH fell and ACTH rose with evidence of fragmentation of pro-gamma-MSH, suggesting that these peptides act in concert in the development of the fetal adrenal cortex and also provide the necessary drive to bring about parturition. In an attempt to explore the pathophysiology of adrenal function we have cloned human POMC cDNA which led to the discovery of a 9bp addition/deletion mutation in the C-terminus of gamma 3-MSH between positions 67-73. Chinese hamster ovary cells (CHO) cells stably transfected with constructs containing the variant POMC cDNAs have shown a degree of partial processing. Work is currently underway to further investigate the effects of these mutations on the processing by the prohormone converting enzymes PC1 and PC2.
阿黑皮素原（POMC）是一种多激素前体，主要在垂体远侧部和中间部产生，在那里它经过组织特异性加工以产生一系列肽。我们之前已经表明，源自POMC N端区域的肽参与大鼠肾上腺的生长。使用特异性双位点免疫放射分析，我们发现17周龄胎羊的血浆中促γ-MSH比促肾上腺皮质激素（ACTH）多50倍。随着足月临近，促γ-MSH水平下降，ACTH水平上升，同时有促γ-MSH片段化的证据，这表明这些肽在胎儿肾上腺皮质发育中协同作用，并且也为分娩提供必要的驱动力。为了探索肾上腺功能的病理生理学，我们克隆了人POMC cDNA，这导致在γ3-MSH C端第67至73位之间发现了一个9bp的插入/缺失突变。用含有变异POMC cDNA的构建体稳定转染的中国仓鼠卵巢（CHO）细胞已显示出一定程度的部分加工。目前正在开展工作以进一步研究这些突变对激素原转化酶PC1和PC2加工的影响。
