Fig 3 - uploaded by Olga Smirnova
Content may be subject to copyright.
Effect of hyperprolactinemia on PRLR expression in renal distal tubules (a) and cholangiocytes in the liver (b) of normal female rats (light bars) and rats with obstructive cholestasis (dark bars). Shaded bars: corresponding group against the background of two-week hyperprolactinemia. *p<0.05 in comparison with the corresponding group without hyperprolactinemia. The number of animals is shown in parentheses.
Source publication
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 recept...
Similar publications
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 hyperprolact...
Citations
... During the evolution, the functions of pro lactin have changed. If in the lower vertebrates, osmoreg ulation is the major prolactin function, in mammals, pro lactin exhibits this function only under pathological con ditions associated with hyperprolactinemia (in particular, in the model of cholestasis of pregnancy), as it has been demonstrated in the studies by our laboratory [4,90,123]. Different kidney structures respond to hyperprolactin emia on the background of obstructive cholestasis by upregulation of PRLR expression [90]. ...
... If in the lower vertebrates, osmoreg ulation is the major prolactin function, in mammals, pro lactin exhibits this function only under pathological con ditions associated with hyperprolactinemia (in particular, in the model of cholestasis of pregnancy), as it has been demonstrated in the studies by our laboratory [4,90,123]. Different kidney structures respond to hyperprolactin emia on the background of obstructive cholestasis by upregulation of PRLR expression [90]. Using experimen tal heart failure model, Tsuchida et al. demonstrated that the expression levels of all PRLR isoforms and the topog raphy of their expression in mouse kidneys could be regu lated by ligation of the abdominal aorta [124]. ...
The review describes functional and structural features of different isoforms of prolactin receptor, mechanisms of signaling pathway activation, and molecular messengers involved in the transmission and termination of signal from the prolactin receptor isoforms. Changes in the ratio between prolactin receptor isoforms, key mediators of prolactin signal transduction and termination in various organs and tissues, are analyzed. Special attention is given to the role of molecular mediators and the ratio between the isoforms in normal physiological functions and pathologies. Approaches for therapeutic correction of prolactin signaling impairments are discussed.
... This cholestasis of pregnancy is associated with poor fetal prognosis due to intoxication. It was shown in our labora tory that additional growth of prolactin concentration was observed in pregnant rats in a cholestasis model, as well as disruption of the water-salt exchange [10]; similar changes were observed by other researchers in pregnant women with this pathology [12 14]. The changes in water-salt exchange can be explained by the fact that the kidney takes over the liver function related to excretion of bile acids and bilirubin during cholestasis. ...
... It is known that the functions of prolactin have changed during evolution. If the osmoregulatory function of prolactin is the main one in the lower vertebrates, in mammals it is only manifested in pathologies accompa nied with hyperprolactinemia (such as the cholestasis of pregnancy model) as shown in this and our previous works [10,15]. The presented study was intended for fol lowing the course of changes of the molecular targets of the prolactin osmoregulatory effect in mammals in com parison with the lower vertebrates. ...
Participation of Na⁺/K⁺-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na⁺/K⁺-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na⁺/K⁺-ATPase measured by Western blotting in the kidney medulla. Decrease in Na⁺/K⁺-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na⁺/K⁺-ATPase. There were no correlations between the Na⁺/K⁺-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na⁺/K⁺-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholesta- sis of pregnancy.
... Cholestasis was modeled by ligation of the common bile duct. HP was induced by transplantation of the donor pituitary under the renal capsule of a recipient [1,2,4], because it was previously shown that obstructive cholestasis is accompanied by HP, while transplantation of the pituitary causes the additional 2-3-fold increase in serum prolactin [4]. ...
We studied possible involvement of prolactin in the regulation of bicarbonate biodynamics using female rat model of cholestasis of pregnancy induced by transplantation of the donor pituitary under the renal capsule of a recipient (hyperprolactinemia) and bile duct ligation (cholestasis). The concentration of bicarbonates in the bile and blood, their excretion, clearance, and reabsorption, as well as glomerular filtration rate and excretion of sodium ions were assessed. It was found that the main effect of prolactin was directed to the kidney-regulated pool of bicarbonates and consisted in stimulation of their clearance and inhibition of reabsorption, which led to a decrease in bicarbonate blood concentration. Parallel influence of prolactin on the clearance of bicarbonates and sodium ions was observed.
... Thus, it seems that HyperPRL results in constant expression of the short PRL receptor and reduced expression of the long PRL receptor at the prostate gland. These results are consistent with those reported for kidney, lymphocytes and ovary [34][35][36][37]. Hence, it is suggested that modification in expression of receptor mRNA could be a consequence of alterations in proteins regulating the alternative splicing process, mainly the SR which is involved in producing the long receptor [36,[38][39][40]. ...
Introduction : Biolasol is a solution developed in Poland for flushing the kidneys, liver, heart and pancreas by simple hypothermia method prior to transplantation. The solution supports the cellular integrity of grafts during ischemia-reperfusion injury (IRI). The aim of the study was to evaluate the impact of the concentration of prolactin added to Biolasol on selected biochemical parameters of kidney injury.
Materials and methods : Biolasol was modified by the addition of prolactin at 1 μg/L, 10 μg/L and 100 μg/L and by ascorbic acid at 0.5 mmol/L. After 2 h and 48 h of storage, the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase enzymes, sodium and potassium concentrations, pH and osmolarity parameters were assessed in the perfusates.
Results : The addition of prolactin to Biolasol significantly improves the biochemical parameters of grafts in the models of rinsing, perfusion and reperfusion of isolated porcine kidneys.
Conclusions : The study indicates the nephroprotective role of Biolasol with the addition of vitamin C and prolactin at a 100 μg/L.
Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.
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.
