Chauvet J, Rouille Y, Chauveau C, Chauvet M T, Acher R
Laboratory of Biological Chemistry, University of Paris VI, France.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11266-70. doi: 10.1073/pnas.91.23.11266.
In contrast to most vertebrate species that possess one oxytocin-like hormone and one vasopressin-like hormone, a few groups, such as marsupials or cartilaginous fishes, are endowed with two peptides of either or both types, suggesting possible gene duplications. We have now isolated two oxytocin-like hormones from the pituitary of the spotted dogfish Scyliorhinus caniculus (suborder Galeoidei). Microsequencing as well as chromatographic and pharmacological comparisons with synthetic peptides show that these peptides are [Asn4,Val8]oxytocin (asvatocin) and [Phe3,Asn4,Val8]-oxytocin (phasvatocin). Asvatocin and phasvatocin display oxytocic activity on rat uterus, about 80 and 5 milliunits per nmol, respectively, and virtually no pressor activity on anesthetized rats. They occur in roughly equal molar amounts in the gland; vasotocin is also present in a proportional amount that is lower by about a factor of 20. In addition to the duality, conservative amino acid substitutions are observed in the two oxytocic peptides in positions 4 (Gln-4-->Asn) and 8 (Leu-8-->Val), when compared with oxytocin. Furthermore, replacement of the isoleucine residue found in position 3 of all other oxytocin-like hormones by phenylalanine in phasvatocin is exceptional; it determines a dramatic decrease of the oxytocic activity. Preservation of the C-terminal-amidated nonapeptide pattern in the 12 vertebrate neurohypophysial hormones known to date suggests that both precursors and processing enzymes have coevolved tightly. On the other hand, whereas the great evolutionary stability of the mature hormones (generally observed in vertebrates) suggests a strict messenger-receptor coevolution, the exceptional diversity found in cartilaginous fishes (six oxytocin-like peptides identified out of eight known) might be due to a looseness of selective constraints, perhaps in relationship with their specific urea osmoregulation.
与大多数拥有一种催产素样激素和一种加压素样激素的脊椎动物物种不同，有少数类群，如袋类动物或软骨鱼类，拥有两种类型中的一种或两种肽，这表明可能发生了基因复制。我们现在从斑点角鲨（Scyliorhinus caniculus， Galeoidei亚目）的垂体中分离出了两种催产素样激素。微量测序以及与合成肽的色谱和药理学比较表明，这些肽是[Asn4,Val8]催产素（天冬催产素）和[Phe3,Asn4,Val8]-催产素（苯丙天冬催产素）。天冬催产素和苯丙天冬催产素对大鼠子宫显示催产活性，分别约为每纳摩尔80和5毫单位，对麻醉大鼠几乎没有升压活性。它们在腺体中的摩尔量大致相等；加压催产素也以成比例的量存在，其含量约低20倍。除了这种二元性外，与催产素相比，在两种催产肽的第4位（Gln-4→Asn）和第8位（Leu-8→Val）观察到保守的氨基酸取代。此外，苯丙天冬催产素将所有其他催产素样激素第3位的异亮氨酸残基替换为苯丙氨酸是例外情况；这导致催产活性急剧下降。在迄今已知的12种脊椎动物神经垂体激素中，C末端酰胺化九肽模式的保留表明前体和加工酶都紧密协同进化。另一方面，虽然成熟激素的巨大进化稳定性（通常在脊椎动物中观察到）表明信使-受体严格协同进化，但软骨鱼类中发现的异常多样性（在已知的8种中有6种催产素样肽被鉴定出来）可能是由于选择性限制的松弛，也许与它们特定的尿素渗透调节有关。
