Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma concentrations of prolactin and estradiol-17 beta were measured by specific radioimmunoassays in 150 women with normal pregnancies and 76 women with cholestasis of pregnancy. At 33 to 34 weeks of gestation plasma prolactin concentrations were 187 +/- 23 ng/ml (mean +/- S.E.M.) for normal pregnancy and 341 +/- 38 ng/ml for cholestasis (p less than 0.001). At 35 to 36 weeks they were 254 +/- 24 and 355 +/- 26 ng/ml (p less than 0.01), and at 37 to 38 weeks 175 +/- 14 and 365 +/- 34 ng/ml (p less than 0.001), respectively. Higher prolactin levels in the cholestasis group were not related to differences in plasma estradiol-17 beta concentrations. No correlation was found between plasma prolactin and serum aminotransferase levels, or between prolactin levels and placental weight. The mechanisms by which plasma prolactin levels become elevated in cholestasis of pregnancy remain to be elucidated.
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PMID:Elevated plasma prolactin concentration in cholestasis of pregnancy. 44 98

Livestock grazing lush Kochia scoparia (L.) Schrad, sometimes experience BW loss, hyperbilirubinemia, photosensitization, and polyuria. Animals fed kochia hay may exhibit milder or negligible signs of toxicosis but fail to utilize nutrients efficiently. To characterize early aspects of kochia toxicosis and to evaluate prospective treatments, 12 wether lambs (34 +/- 3 kg) were fed prebloom kochia hay (83% OM, 15% CP, and 6.3% total oxalate) and treated as follows: 1) no treatment; 2) drenched daily with aqueous ZnSO4 to provide 30 mg of Zn/kg of BW); 3) injected i.p. twice weekly with N-acetyl-L-cysteine (CYS) in saline (21 mg/kg of BW) plus trans-stilbene oxide (TSO) in corn oil (27 mg/kg of BW); and 4) treated as 2) plus 3). Treatments were imposed factorially (2 x 2) with three lambs per treatment. Kochia intake (ad libitum) averaged .57 kg/d (1.7% of BW) for 80 d, and digestibility of DM and CP were 44 and 59%, respectively, at wk 4, but BW loss was severe (6 to 11 kg/lamb). After 14 d, serum insulin and prolactin were decreased (P less than .05) below initial values (.48 to .11 and 102 to 28 ng/ml, respectively). Serum somatotropin increased (P less than .05) from 4.5 to 6.8 ng/ml at 4 wk. Serum total bilirubin increased threefold at 3 wk (P less than .05) and declined slightly thereafter through 10 wk. Early changes in serum enzymes reflected mild hepatotoxicosis without cholestasis, whereas histopathology (at 80 d) showed diffuse hepatocyte swelling and nephrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered metabolic hormones, impaired nitrogen retention, and hepatotoxicosis in lambs fed Kochia scoparia hay. 188 2

To evaluate whether intravenous injection of dehydroepiandrosterone sulfate (DHEAS), by enhancing estradiol (E2) production, would stimulate prolactin (PRL) secretion in late pregnancy, maternal serum PRL was determined before and 1 to 5 hours after administration of 100 mg of DHEAS in a total of 41 women with normal or complicated late pregnancies (twin pregnancy, pre-eclampsia, intrahepatic cholestasis of pregnancy, diabetes). The basal serum PRL concentration in patients with diabetes was significantly lower than normal. The mean PRL level did not change significantly in any group in spite of the increase in serum E2 levels after the DHEAS injection. The lack of PRL response to a rapid rise in E2 may be due to the maximal inhibition of the PRL-inhibiting factor in the hypothalamus and/or maximal activation of the pituitary lactotrophs occasioned by the high estrogen environment during late pregnancy.
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PMID:Stable prolactin level after enhanced estradiol production following dehydroepiandrosterone sulfate. 644 2

The role ofprolactin receptor isoforms in discrimination ofprolactin effects on liver is summarized. The necessity of studying of parameters ofprolactin receptor expression in differentially isolated different types of liver cells is demonstrated. The review is illustrated by data on different regulation by sex hormones and obstructive cholestasis of expression of prolactin receptor isoforms in rat hepatocytes and epithelial cells of bile ducts. The mathematical model is introduced for estimation of intensity of prolactin-induced signal cascades on the basis of experimentally measured parameters of prolactin receptor expression. Some further steps of the investigation of prolactin effects discrimination at the level receptor unit are suggested.
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PMID:[Mechanisms of discrimation of the prolatin physiologic action on the liver at the receptor level of hepatocytes and cholangiocytes]. 1583 42

Prolactin participates in the regulation of liver function. However, prolactin receptor (PrlR) expression and its regulation have been described only for hepatocytes. In this study, we investigated the expression and regulation of PrlR isoforms in the other important intrahepatic cellular compartment: the biliary epithelial cells, or cholangiocytes. Our aim was to determine whether prolactin should be considered as a potential regulator of cholangiocyte function under normal and pathological conditions. Cholangiocytes and hepatocytes were differentially isolated from rat liver. PrlR expression was analysed at the mRNA level by isoform-specific semiquantitative PCR, and at the protein level by immunostaining of liver sections. Hormonal regulation of PrlR expression was evaluated by comparing intact rats with gonadectomized, pituitary-grafted or bromocriptine-treated animals. Common bile-duct ligation was used as the experimental model of cholestasis. Our results demonstrate that the expression pattern and regulation of PrlR isoforms is totally different in cholangiocytes compared with hepatocytes: (1) mature rat cholangiocytes express low levels of PrlR, while it is very high in hepatocytes, (2) only the long isoform is detected in cholangiocytes, while the short isoform predominates in hepatocytes and (3) PrlR levels in cholangiocytes are induced by obstructive cholestasis, but not by sex hormones or prolactin, while it is the opposite in hepatocytes. From these data, the actions of prolactin on liver are anticipated to exhibit strong cell-type specificity in both normal and pathological conditions.
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PMID:Long isoform of prolactin receptor predominates in rat intrahepatic bile ducts and further increases under obstructive cholestasis. 1646 60

The presence of prolactin receptor and peculiarities of its isoform expression in bile duct cells (cholangiocytes) differentially isolated from rat liver under different conditions were investigated in the present study. Normal cholangiocytes express prolactin receptor at relatively low level comparable to those of some prolactin-dependent tissues. Long receptor isoform is predominant in cholangiocytes but not in hepatocytes. The prolactin receptor level increases significantly under obstructive cholestasis due to evaluation of long and appearance of short isoforms. In rat cholangiocytes, unlike other tissues, the main positive regulators of prolactin receptor expression are cholestasis-induced factors instead of sex hormone and prolactin levels. Long isoform is predominant and induced primarily by cholestasis-induced factors.
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PMID:Prolactin receptors in rat cholangiocytes: regulation of level and isoform ratio is sex independent. 1648 23

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.
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PMID:Manifestation of multidrug resistance protein 3 (MRP3) in liver and kidney cells in cholestasis: effects of hyperprolactinemia. 2348 93

Silymarin is a bioflavonoid complex extract derived from dry seeds of Milk thistle [(Silybum marianum(L.) Gaemrnt. (Fam. Asteraceae/Compositaceae)] whose hepatoprotective effect has clinically been proved. Low toxicity, favorable pharmacokinetics, powerful antioxidant, detoxifying, preventive, protective and regenerative effects and side effects similar to placebo make silymarin extremely attractive and safe for therapeutic use. The medicinal properties of silymarin and its main component silibinin have been studied in the treatment of Alzheimer's disease, Parkinson's disease, sepsis, burns, osteoporosis, diabetes, cholestasis and hypercholesterolemia. Owing to its apoptotic effect, without cytotoxic effects, silymarin possesses potential applications in the treatment of various cancers. Silymarin is being examined as a neuro-, nephro- and cardio-protective in the damage of different etiologies due to its strong antioxidant potentials. Furthermore, it has fetoprotective (against the influence of alcohol) and prolactin effects and is safe to be used during pregnancy and lactation. Finally, the cosmetics industry is examining the antioxidant and UV-protective effects of silymarin. Further clinical studies and scientific evidence that silymarin and silibinin are effective in the therapy of various pathologies are indispensable in order to confirm their different flavonolignan pharmacological effects.
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PMID:New therapeutic potentials of milk thistle (Silybum marianum). 2455 2

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.
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PMID:Manifestation of cystic fibrosis transmembrane regulator (CFTR) in hepatic ductal structures and renal tubules of female rats with experimental cholestasis of pregnancy. 2477 Jul 51

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.
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PMID:Effect of prolactin on the water-salt balance in rat females in the model of cholestasis of pregnancy. 2482 2


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