Yamamoto M, Matsui N
Nihon Naibunpi Gakkai Zasshi. 1978 Mar 20;54(3):187-202. doi: 10.1507/endocrine1927.54.3_187.
Most of the cortisol in circulating blood is bound to proteins (transcortin and albumin), and the rest is protein-unbound. It has generally been accepted that transcortin-bound cortisol (Tr-F) and albumin-bound cortisol (Al-F) are physiologically inactive, and that protein-unbound cortisol (U-F) is active. It is also known that the binding capacity of transcortin to cortisol is lower at 37 degrees C than at 4 degrees C. However, no investigations concerning the influence of temperature changes the physiological range have been reported, probably because of the lack of proper methods. In this report, the influence of temperature changes the physiological range on serum protein-cortisol binding is assessed and its physiological roles are discussed. Cortisol binding of transcortin and albumin was determined by a newly developed isocolloidosmolar equilibrium dialysis method. The total cortisol concentration was determined by the CPB assay method described by Murphy. In the beginning, experiments were performed using pooled human serum. This serum was dialyzed at 35, 37, 39 and 41 degrees C. U-F and Al-F concentrations increased in accordance with the increment of incubation temperature, whereas Tr-F concentration decreased. The association constant of transcortin to cortisol decreased with the rise of incubation temperature. It was 3.43, 2.92, 2,32 and 1.66 X 10(7)M-1 at 35, 37, 39 and 41 degrees C, respectively. However, the association constant of albumin to cortisol was 3.04 X 10(3)M-1 and stayed unchanged under these conditions. These results suggest that the transcortin-cortisol complex dissociates with temperature rises and that a part of freed cortisol is bound to albumin while the other part remains protein-unbound cortisol. When various amounts of cortisol were added to the pooled human serum, which was dialyzed at 35, 37, 39 and 41 degrees C; U-F, Al-F and Tr-F concentrations increased corresponding to the amount of added cortisol. The increase of U-F, Al-F concentrations and decrease of Tr-F concentration induced by the rise of temperature was still significant at each total coritsol concentration. Cortisol fractions in the serum of healthy subjects were compared with those of 39 febrile patients consisting of A group (body temperature 37 approximately 38 degrees C), B group (38 approximately 39 degrees C), and C group (39 approximately 40 degrees C). Total cortisol concentrations increased with the rise of body temperature. They were 7.62 (normal), 10.64 (A), 14.84 (B) and 21.37 (C) microgram/100ml, respectively. U-F% and Al-F% increased parallel with the total cortisol concentration. Tr-F%, binding capacity of transcortin. These results reveal that the rise of body temperature elevates the total cortisol concentration, and the greater part of increased cortisol becomes U-F and Al-F, while a relatively small part of it is bound to transcortin. The percent change of the total cortisol concentration in comparison with healthy subjects was 150 (A), 209 (B) and 593 (C), respectively...
循环血液中的大部分皮质醇与蛋白质(皮质素转运蛋白和白蛋白)结合,其余部分未与蛋白质结合。一般认为,与皮质素转运蛋白结合的皮质醇(Tr-F)和与白蛋白结合的皮质醇(Al-F)无生理活性,而未与蛋白质结合的皮质醇(U-F)具有活性。还已知皮质素转运蛋白与皮质醇的结合能力在37℃时低于4℃时。然而,尚未有关于温度在生理范围内变化影响的研究报道,可能是由于缺乏合适的方法。在本报告中,评估了温度在生理范围内变化对血清蛋白 - 皮质醇结合的影响,并讨论了其生理作用。通过新开发的等胶体渗透压平衡透析法测定皮质素转运蛋白和白蛋白的皮质醇结合情况。总皮质醇浓度通过墨菲描述的CPB测定法测定。起初,使用混合人血清进行实验。该血清在35、37、39和41℃下进行透析。U-F和Al-F浓度随着孵育温度的升高而增加,而Tr-F浓度降低。皮质素转运蛋白与皮质醇的结合常数随着孵育温度的升高而降低。在35、37、39和41℃时分别为3.43、2.92、2.32和1.66×10⁷M⁻¹。然而,白蛋白与皮质醇的结合常数为3.04×10³M⁻¹,在这些条件下保持不变。这些结果表明,皮质素转运蛋白 - 皮质醇复合物随着温度升高而解离,释放出的皮质醇一部分与白蛋白结合,而另一部分仍为未与蛋白质结合的皮质醇。当向在35、37、39和41℃下透析的混合人血清中加入不同量的皮质醇时;U-F、Al-F和Tr-F浓度相应于加入的皮质醇量而增加。在每个总皮质醇浓度下,温度升高引起的U-F、Al-F浓度增加和Tr-F浓度降低仍然显著。将健康受试者血清中的皮质醇组分与39例发热患者的血清进行比较,这些发热患者分为A组(体温37~38℃)、B组(38~39℃)和C组(39~40℃)。总皮质醇浓度随着体温升高而增加。它们分别为7.62(正常)、10.64(A)、14.8(B)和21.37(C)微克/100毫升。U-F%和Al-F%与总皮质醇浓度平行增加。Tr-F%,即皮质素转运蛋白的结合能力。这些结果表明,体温升高会提高总皮质醇浓度,增加的皮质醇大部分变为U-F和Al-F,而相对较小的一部分与皮质素转运蛋白结合。与健康受试者相比,总皮质醇浓度的变化百分比分别为150(A)、209(B)和593(C)……