Kontula K, Jänne O, Vihko R, de Jager E, de Visser J, Zeelen F
Acta Endocrinol (Copenh). 1975 Mar;78(3):574-92. doi: 10.1530/acta.0.0780574.
Progesterone-binding proteins from human, rabbit, sheep and guinea pig myometrial cytosol, all induced with oestradiol, as well as from pregnant guinea pig myometrium and plasma were investigated. The physico-chemical properties of the oestradiol-induced binding proteins were very similar in all the species studied. In all, 63 steroids were tested for their ability to compete with tritiated progesterone for the binding sites on these six proteins and their relative affinities were determined. The studies reveal that the ligand specificities of oestrogen-induced myometrial binding proteins from human, rabbit and sheep are rather similar, whereas that from guinea pig myometrium has different binding characteristics. The properties of the binding proteins from pregnant guinea pig uterus and plasma differ substantially from all of the induced proteins. It is clear from the different physico-chemical characteristics and binding specificities that the oestrogen-induced myometrial protein of the guinea pig is not the same as that which appears in the myometrium and plasma during pregnancy. The binding energies of the well bound progestational compounds were of the order of -12 Kcal/mole, half of which stems from the interaction of the steroid nucleus with the protein. The specific interaction of the protein with the two functional groups, the 3-keto-4-ene system and the acetyl sid chain each contributed-3 Kcal/mole. In the case of the rabbit, sheep and human proteins a 17alpha-ethynyl-17beta-hydroxyl function could replace the acetyl side chain. For a large number of steroids reasonable agreement existed between the degree of binding to the rabbit myometrial protein and in vivo biological activity (Clauberg-McPhail test) in the same species. The data suggest that as far asthe binding aspect is concerned, the rabbit is an appropriate model for assessing the biological activity of compounds under development for human application. The in vitro binding system is also a useful tool to assess whether steroids need to be bio-activated before eliciting a biological response.
对来自人、兔、绵羊和豚鼠子宫肌层胞质溶胶的孕酮结合蛋白进行了研究，这些蛋白均由雌二醇诱导产生，同时还研究了来自怀孕豚鼠子宫肌层和血浆的孕酮结合蛋白。在所研究的所有物种中，雌二醇诱导的结合蛋白的物理化学性质非常相似。总共测试了63种类固醇与氚化孕酮竞争这六种蛋白上结合位点的能力，并确定了它们的相对亲和力。研究表明，人、兔和绵羊的雌激素诱导子宫肌层结合蛋白的配体特异性相当相似，而豚鼠子宫肌层的结合蛋白具有不同的结合特性。怀孕豚鼠子宫和血浆中的结合蛋白性质与所有诱导蛋白有很大不同。从不同的物理化学特征和结合特异性可以明显看出，豚鼠雌激素诱导的子宫肌层蛋白与怀孕期间子宫肌层和血浆中出现的蛋白不同。结合良好的孕激素化合物的结合能约为-12千卡/摩尔，其中一半来自类固醇核与蛋白质的相互作用。蛋白质与两个官能团（3-酮-4-烯系统和乙酰侧链）的特异性相互作用各贡献-3千卡/摩尔。就兔、绵羊和人蛋白而言，17α-乙炔基-17β-羟基官能团可以取代乙酰侧链。对于大量类固醇，其与兔子宫肌层蛋白的结合程度与同一物种体内生物活性（克劳伯格-麦克费尔试验）之间存在合理的一致性。数据表明，就结合方面而言，兔是评估正在开发用于人类应用化合物生物活性的合适模型。体外结合系统也是评估类固醇在引发生物反应之前是否需要进行生物活化的有用工具。
