Effects of testosterone on bile acid composition of bile male rats

I. S. Chernuha, E. M. Reshetnik, N. E. Nurishchenko, S. P. Veselsky

Abstract


Introduction. Androgens, particularly testosterone, are well known regulators of metabolic processes in the organism. Testosterone affects carbohydrate and lipid metabolism in liver cells. The risk of fatty liver and nonalcoholic hepatitis, cirrhosis, hepatocellular carcinoma depends on the level of testosterone in the blood. The mechanisms of the effects of testosterone in normal and pathological conditions are not sufficiently clarified. In particular the effects of androgens on the metabolic transformation and secretion of specific components of bile – bile acids remain poorly understood. It is known the significant differences in bile formation and biliary excretion in individuals of different sexes.

Purpose. The main aim of our research was to study effects of testosterone on the bile acids composition of bile in male rats.

Methods. Bile duct cannulated in acute experiments on male rats (0,18-0,27 kg, n = 12). Rats were under sodium thiopental anesthesia (60 mg / kg) in acute experiments. Testosterone propionate (0,7 mg / kg, intraportal) injected after taking the first half-hour sample of bile (baseline). The next five half-hour bile samples collected after administration of testosterone. In each sample of bile concentration of separate bile acids fractions were determined using modified in our laboratory TLC method. Separate bile acids fractions that were used in our work are: conjugated bile acids (taurocholate, taurochenodeoxycholate and taurodeoxycholate, glycocholate, glycochenodeoxycholate and glycodeoxycholate) and free bile acids (cholate, chenodeoxycholate and deoxycholate).

Results. It was found that testosterone propionate caused a biphasic effect on the content of conjugated (glycochenodeoxycholate and glycodeoxycholate) and free (chenodeoxycholate and deoxycholate) bile acids in the bile of male rats. First, this bile acids concentration increased (compared with control values) immediately after the testosterone propionate introduction. So concentration of this specific bile components in the liver secret decreased (compared with control values) after 2,5 hours after administration of hormone. The concentration of other fractions of bile acids decreased significantly after 2-2,5 hours after hormone. The most significant reduction of cholates in male rats bile founded in bile sample collected in the last half-hour interval acute experiment (two hours after intraportal hormone administration). Taurocholic acid concentration decreased by 19,2% (p <0,01), taurochenodeoxycholic and taurodeoxycholic – by 22,6% (p <0,01), glycocholic – 40% (p <0,01), glycochenodeoxycholi and glycodeoxycholic – by 29,9% (p <0,01), cholic acid – by 20,5%     (p <0,05), and chenodeoxycholic and deoxycholic acids – on 41,4% (p <0,01).

Originality. We have found that concentration of the conjugated and free bile acids in the bile of male rats significstly change under the influence of the testosterone propionate. It was established that hormone (single intraportal injection in acute experiment) had an inhibitory effect on the process of conjugation of bile acids (bile acids conjugation). But testosterone propionate didn’t influrnced on bile acids hydroxylation in the liver of male rats. Thus, in our experiments testosterone affects the content of all studied fractions of the bile acids in the bile of male rats. Mechanisms of testosterone action secretion of bile acids require further research.

Conclusion. Testosterone propionate (0,7 mg / kg, intraportal single dose in acute experiment) reveals a biphasic effect on the content of the glycochenodeoxycholic, glycodeoxycholic, chenodeoxycholic and deoxycholic acids  in the male rats bile. Immediately after the introduction of the hormone concentration of the bile acids increases and at the end of the experiment (after 2-2.5 hours after administration of testosterone) their content in the bile is reduced compared to the control rats. Concentrations of the taurocholic, taurochenodeoxycholic, taurodeoxycholic, glycocholic, cholic acids in male rats bile decreased after 2-2,5 hours after hormone introduction. The most significant decreasing of the bile acids concentration in the male rats bile was found in the bile sample collected in the last half-hour interval acute experiment, ie 2-2.5 hours after testosterone propionate administration. 


Keywords


testosteron; bile; bile acids

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