[The effect of ultra small doses of thyroliberin on the structural changes in endoplasmic reticulum membranes in vitro]

Abstract

Peptides are known to have the ability of modulating the activity of important regulatory cellular systems. One of them--thyroliberin, i.e. thyreotropin-releasing hormone (TRH), causes changes in the membrane structure and morphology of rat erythrocytes, as well as activates retractive activity of lymphatic vessels in ultra low concentrations (10(-10) to 10(-16) mol/l). In this study we used an electron spin resonance (ESR) method to explore the effect of TRH in a wide range of concentrations (10(-4) to 10(-18) mol/l) on thermo-induced structural transitions and microviscosity of lipid bilayer of the endoplasmic reticulum membrane of mice (C57 bI) liver cells. Two stable free radicals were used as paramagnetic probes: 2,2,6,6-tetramethil-4-capryolyl-1-oxyl and 16-doxyl-stearic acid, that are localized in superficial and deep layers of the membrane respectively. TRH caused a statistically significant change (p < 0.001) in microviscosity of the membrane surface layer. The largest effect (up to 30% decrease) was observed at TRH concentrations of 10(-10) and 10(-16) mol/l. It was also demonstrated that an addition of 10(-4), 10(-10) and 10(-16) mol/l of TRH decreases effective activation energy and temperature (by several degrees) of the thermo-induced structural transitions. The observed changes in the parameters of the membrane surface layer induced by TRH may be essential for its physiological activity, because of the obtained negative correlation (r = 0.99; p < 0.001) between the membrane microviscosity and frequency of lymphatic vessels' contraction. Complex changes in the structure of deep hydrophobic layer of the membrane caused by TRH were observed in this study as well. Higher concentrations of TRH (10(-4) and 10(-10) mol/l) produced results that were similar to the effect of TRH on the superficial lipid layer of the membrane, whereas the effect of ultra low TRH concentration (10(-16) mol/l) was reversed for microviscosity, number and activation energy of structural transitions in contrast with the case of surface layer. The results of this study suggest presence of a nonspecific factor in the effect of TRH on structural characteristics of the lipid component of biological membranes. It is possible, that the change of structural properties of biological membranes may be a part of the mechanism of TRH action at ultra low concentrations.