Chernukha I. Effect of testosterone on the bile secretory function of rat liver

The study of sex differences in the regulation of bile secretory function is considered to be one of the current trends in hepatology. This is because there is a functional relationship between the hepatobiliary and reproductive systems. The liver acts as a intermediator in a number of systemic effects of sex hormones on the body and is a key organ for their metabolism. Significant inter-sex differences of bile formation in liver tissue necessitate thorough experimental studies of the effect of testosterone in various tests on the composition of bile and the ratio of the cholates of the liver secretion of different sex species. And, since sex steroids are capable of regulating the bile secretory function of the liver, their deficiency or excess may play a key role in the appearance of cholesterol gallstones. Therefore, considerable attention is now being paid to the study of the role of androgens in the development of pathologies of the hepatobiliary system. Since hormones of a steroidal nature are considered to be one of the chains of effector mechanisms by which homeostasis is provided and processes of tissue proliferation, differentiation and growth occur, the relationship between the concentration of steroid hormones can determine the direction of physiological processes and their possible disorders. The purpose of the study was to research the role of testosterone in the regulation of bile secretory liver function. In the acute experiments testosterone was singly injected into the portal vein of the liver at a rate of 700 mcg kg of the animal body weight, or intramuscularly daily for 5 days. To determine the role of androgen receptors in the regulation of chole-secretion, animals were intragastrally injected an androgen inhibitor flutamide receptor at a dose of 25 mg kg of the animal body weight. The results of the study indicate a corrective effect of testosterone on the bile secretory function of rat liver in both sexes. The changes in the composition of bile after intra-portal and intramuscular administration of testosterone are different in male and female rats. Testosterone in intra-portal administration caused a decrease in the volume rate of bile secretion in male rats, and increasing of female bile flow two hours after hormone administration. Inhibition of choleresis by intra-portal administration of testosterone is accompanied by decrease of concentration of taurocholate, glycocholate, dihydroxycholane tauro- and glycoconjugates of bile acids in the hepatic secretion of the rat males. On the other hand, the content of taurocholate and glycocholate increased in female bile indicating increasing of the conjugation of bile acids with taurine and glycine and biotransformation of bile acids. Moreover hormone reduced the concentration of free fatty acids, phospholipids and free cholesterol in bile, indicating the changing of metabolism in the liver cells. The revealed differences in the bile secretory function of the liver in male and male rats for the same dose of the hormone preparation is largely due to the significant difference in animals of different sex, both testosterone level and expression of the corresponding receptors in different tissues, including the liver. During the course of intramuscular administration of testosterone, both males and females intensified choleresis. In males bile concentration of all taurocholates and glycocholates was increased, but in females the content of the conjugated bile acids increased, which generally indicates increasing of the efficiency of enzymes involved in the exchange of the bile acids in liver cells under the influence of the hormone dose tested. Blockade of the testosterone receptors by intragastric administration of flutamide decreases the bile secretion rate of male rats and inhibits the formation and flow of the bile acid glycoconjugates into the bile ducts, indicating the inhibitory effect of flutamide on the biosynthesis and transport of glycocholates in the liver. The influence of flutamide decreased the ratio of phospholipids to cholesterol, which may be associated with an increase in the content of endogenous androgens and products of their subsequent metabolic transformation ̶ estrogens in the use of a nonsteroidal testosterone receptor inhabitor in the study scheme.