Studies by the immunohistochemical method with semiquantitative analysis of images showed that hyperprolactinemia stimulated CFTR protein manifestation in the bile ducts of female rats, which was clearly expressed in experimental cholestasis of pregnancy. The expression of CFTR in the renal tubules was reduced in hyperprolactinemia under conditions of normal liver function and in cholestasis of pregnancy. Significant positive correlations between CFTR, prolactin receptor, and multiple drug resistance protein 3 were detected in the bile ducts, but not in the renal tubules. Presumably, prolactin has a direct effect on CFTR expression in the bile ducts and indirect effect in the renal tubules. Changes in CFTR protein manifestation in the hepatic ductal structures and renal tubules in experimental pregnancy cholestasis could aggravate the disease.
Immunohistochemistry with semiquantitative image analysis showed that cholestasis induced an increase in the manifestation of mrp3 in cholangiocytes of female rats, but did not affect this parameter in the studied structures of kidney. Under conditions of normal liver function, mrp3 expression in cholangiocytes was also elevated during hyperprolactinemia. Expression of mrp3 in cholangiocytes directly correlated with prolactin receptor expression. In cholestasis, prolactin increased mrp3 manifestation of only in the distal renal tubules. Thus, mrp3 manifestation increases in liver cells, but remains unchanged in kidney cells. The hyperprolactinemia-induced changes in the mrp3 levels and their correlations with prolactin receptor expression were shown to differ in the kidney and liver cells. It was hypothesized that prolactin produced a direct effect on mrp3 expression in cholangiocytes.
Immunohistochemistry with semiquantitative image analysis showed that prolactin receptor in distal renal tubules of female rats is most sensitive to the negative effects of both cholestasis and hyperprolactinemia. The responses of medullary tubules to cholestasis and hyperprolactinemia were less pronounced: decrease and increase in prolactin receptor expression, respectively. Proximal tubules were characterized by stable levels of prolactin receptor expression insensitive to the effects of obstructive cholestasis and hyperprolactinemia. The cholestasis-induced changes in the intensity of prolactin receptor expression were opposite in kidney and liver cells. It is concluded that different parts of the nephron differ by the presence, type, and direction of regulation of prolactin receptor expression in obstructive cholestasis and hyperprolactinemia.
Immunohistochemistry with semi-quantitative analysis of computer images showed that prolactin receptor and cystic fi brosis transmembrane regulator (CFTR) in cholangiocytes of female rats elevated in cholestasis quickly respond to its relief. The effect of hyperprolactinemia on the extent of return of these proteins to baseline was different. Decompression of the bile duct abolishes the negative effect of hyperprolactinemia on CFTR expression and its positive effect on mrp3 expression in the proximal renal tubules. In renal medulla, mrp2 expression decreased when cholestasis was induced against the background of hyperprolactinemia and increases after its removal. Prolactin receptors and CFTR in cholangiocytes are most susceptible to the decrease in bile duct pressure. Changes in the expression of the studied proteins after cholestasis relief are apparently associated with attenuated toxicity of the products removed by the kidneys, which abolishes the effects of prolactin.
Using immunohistochemical method with semiquantitative analysis of images, we showed that mrp2 expression in response to cholestasis decreased in hepatocytes and cholangiocytes, and remained unchanged in the kidney structures. A decrease of mrp2 expression in renal tubules leading to a decrease of metabolic intoxication of the kidney was demonstrated in cholestasis of pregnancy model. In bile ducts cells, negative correlations of mrp2 with previously measured levels of prolactin receptors, CFTR, and mrp3 were revealed. In renal structures and in hepatocytes, no correlations were found between the expression of these proteins. We hypothesize that prolactin produces a direct effect on mrp2 expression in bile ducts cells mediated by prolactin receptors in cholangiocytes. The absence of correlations between mrp2 and the above-mentioned proteins in hepatocytes and renal structures is most likely related to prolactin effects on other systemic regulators.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.