ABSTRACT
We studied the possibility of prolactin involvement in the regulation of water-salt metabolism in female rats in the model of cholestasis of pregnancy. For simulation of the prolactin level during pregnancy, hyperprolactinemia was simulated by transplantation the pituitary under the renal capsule of the recipient; for modeling cholestasis of pregnancy, a combination of induced hyperprolactinemia and bile duct obstruction was used. Diurnal diuresis, expression of aquaporin 1-4 mRNA in the renal medulla, glomerular filtration rate, and diurnal sodium excretion were evaluated in these models. Diuretic and natriuretic effects of prolactin in the model of cholestasis of pregnancy were demonstrated. These data and the fact that prolactin has no effect on glomerular filtration rate and aquaporin expression suggest that prolactin modulates activity of sodium transporters in the kidney.
Subject(s)
Cholestasis, Intrahepatic/drug therapy , Cholestasis, Intrahepatic/metabolism , Pregnancy Complications/drug therapy , Pregnancy Complications/metabolism , Prolactin/pharmacology , Water-Electrolyte Imbalance/drug therapy , Animals , Aquaporins/metabolism , Cholestasis , Diuretics/pharmacology , Female , Glomerular Filtration Rate , Kidney Medulla/metabolism , Natriuretic Agents/pharmacology , Oligonucleotides/genetics , Pituitary Gland/transplantation , Pregnancy , Rats , Real-Time Polymerase Chain Reaction , Sodium/metabolism , Statistics, NonparametricABSTRACT
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.
Subject(s)
Cholestasis, Intrahepatic/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Hepatic Duct, Common/metabolism , Kidney Tubules/metabolism , Pregnancy Complications/metabolism , Animals , Animals, Outbred Strains , Cholestasis, Intrahepatic/pathology , Female , Hepatic Duct, Common/pathology , Pregnancy , Pregnancy Complications/pathology , Rats , Receptors, Prolactin/metabolismABSTRACT
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.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B/metabolism , Cholestasis/metabolism , Hyperprolactinemia/metabolism , Hyperprolactinemia/physiopathology , Kidney/metabolism , Liver/metabolism , Animals , Female , RatsABSTRACT
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.
Subject(s)
Cholestasis/metabolism , Gene Expression Regulation/physiology , Hyperprolactinemia/metabolism , Kidney Tubules, Distal/metabolism , Receptors, Prolactin/metabolism , Animals , Enzyme-Linked Immunosorbent Assay , Female , Immunoenzyme Techniques , Immunohistochemistry , Kidney Tubules, Proximal/metabolism , Liver/metabolism , Rats , Statistics, NonparametricABSTRACT
Gender-related differences in bilirubin concentration in post-cholestatic bile, bile excretion from the liver, and bile flow velocity disappeared in hyperprolactinemia in the presence of obstructive cholestasis. Gender-related differences in the alternative routes of bilirubin excretion appeared.
Subject(s)
Bilirubin/metabolism , Cholestasis/physiopathology , Hyperprolactinemia/physiopathology , Animals , Bile , Bile Ducts , Female , Ligation , Liver/physiopathology , Male , Rats , Sex FactorsABSTRACT
The effect of hyperprolactinemia on bile excretion from the liver of female rats was shown to increase significantly during obstructive cholestasis. The observed changes were biphasic: initial increase in bilirubin release of into the bile was followed by its reduction. Under conditions of obstructive cholestasis, hyperprolactinemia had a negative effect on the recovery of bile flow rate during decompression of the duct (up to complete cessation of bile flow).
Subject(s)
Bile/metabolism , Cholestasis/physiopathology , Hyperprolactinemia/metabolism , Liver , Prolactin/pharmacology , Animals , Bilirubin/metabolism , Female , Liver/drug effects , Liver/metabolism , Liver/physiopathology , RatsABSTRACT
Experiments on rats revealed sex-related differences in bilirubin concentration in the bile and bile flow rate against the background of obstructive cholestasis. These differences disappeared after gonadectomy. There were no sex-related differences in the rate of bilirubin excretion with the bile after removal of cholestasis, which was attained through different mechanisms in males and females.
