Steroid receptors and heat-shock proteins in patients with primary biliary cirrhosis

Jorge, A. D.

doi:10.1016/0270-9139(93)90465-y

Cited by 3 publications

(4 citation statements)

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“…Supporting our findings, a number of studies have shown the presence of functional ARs in liver cells, including hepatocytes and bile ducts from PBC patients (26,29,38). Also, the AR mRNA has been detected in human liver biopsy samples, fetal liver, and HepG2 cells (48).…”

Section: Discussionsupporting

confidence: 88%

Castration inhibits biliary proliferation induced by bile duct obstruction: novel role for the autocrine trophic effect of testosterone

Yang

Priester²,

Onori

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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S. Castration inhibits biliary proliferation induced by bile duct obstruction: novel role for the autocrine trophic effect of testosterone. Am J Physiol Gastrointest Liver Physiol 301: G981-G991, 2011. First published September 8, 2011; doi:10.1152/ajpgi.00061.2011.-Increased cholangiocyte growth is critical for the maintenance of biliary mass during liver injury by bile duct ligation (BDL). Circulating levels of testosterone decline following castration and during cholestasis. Cholangiocytes secrete sex hormones sustaining cholangiocyte growth by autocrine mechanisms. We tested the hypothesis that testosterone is an autocrine trophic factor stimulating biliary growth. The expression of androgen receptor (AR) was determined in liver sections, male cholangiocytes, and cholangiocyte cultures [normal rat intrahepatic cholangiocyte cultures (NRICC)]. Normal or BDL (immediately after surgery) rats were treated with testosterone or antitestosterone antibody or underwent surgical castration (followed by administration of testosterone) for 1 wk. We evaluated testosterone serum levels; intrahepatic bile duct mass (IBDM) in liver sections of female and male rats following the administration of testosterone; and secretin-stimulated cAMP levels and bile secretion. We evaluated the expression of 17␤-hydroxysteroid dehydrogenase 3 (17␤-HSD3, the enzyme regulating testosterone synthesis) in cholangiocytes. We evaluated the effect of testosterone on the proliferation of NRICC in the absence/presence of flutamide (AR antagonist) and antitestosterone antibody and the expression of 17␤-HSD3. Proliferation of NRICC was evaluated following stable knock down of 17␤-HSD3. We found that cholangiocytes and NRICC expressed AR. Testosterone serum levels decreased in castrated rats (prevented by the administration of testosterone) and rats receiving antitestosterone antibody. Castration decreased IBDM and secretinstimulated cAMP levels and ductal secretion of BDL rats. Testosterone increased 17␤-HSD3 expression and proliferation in NRICC that was blocked by flutamide and antitestosterone antibody. Knock down of 17␤-

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Section: Discussionsupporting

confidence: 88%

Castration inhibits biliary proliferation induced by bile duct obstruction: novel role for the autocrine trophic effect of testosterone

Yang

Priester²,

Onori

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…1B). Low-level expression of the progesterone receptor was expected in hepatocytes (36). Similarly, progesterone receptors (PR, PGRMC1, and PGRMC2) were expressed by male NRC (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Bar ϭ 20 m. B: immunohistochemistry for progesterone receptors (PR, PGRMC1, and PGRMC2) in liver secretion from normal and BDL female male rats confirms receptor expression by bile ducts. Low-level expression of the progesterone receptor was expected in hepatocytes (36). C: by immunofluorescence, progesterone receptors (PR, PGRMC1, and PGRMC2) were expressed by normal rat intrahepatic cholangiocyte cultures (NRC).…”

Section: Methodsmentioning

confidence: 99%

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

Glaser¹,

DeMorrow²,

Francis³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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During cholestatic liver diseases, cholangiocytes express neuroendocrine phenotypes and respond to a number of hormones and neuropeptides by paracrine and autocrine mechanisms. We examined whether the neuroendocrine hormone progesterone is produced by and targeted to cholangiocytes, thereby regulating biliary proliferation during cholestasis. Nuclear (PR-A and PR-B) and membrane (PRGMC1, PRGMC2, and mPRα) progesterone receptor expression was evaluated in liver sections and cholangiocytes from normal and bile duct ligation (BDL) rats, and NRC cells (normal rat cholangiocyte line). In vivo, normal rats were chronically treated with progesterone for 1 wk, or immediately after BDL, rats were treated with a neutralizing progesterone antibody for 1 wk. Cholangiocyte growth was measured by evaluating the number of bile ducts in liver sections. The expression of the progesterone synthesis pathway was evaluated in liver sections, cholangiocytes and NRC. Progesterone secretion was evaluated in supernatants from normal and BDL cholangiocytes and NRC. In vitro, NRC were stimulated with progesterone and cholangiocyte supernatants in the presence or absence of antiprogesterone antibody. Aminoglutethimide was used to block progesterone synthesis. Cholangiocytes and NRC express the PR-B nuclear receptor and PRGMC1, PRGMC2, and mPRα. In vivo, progesterone increased the number of bile ducts of normal rats, whereas antiprogesterone antibody inhibited cholangiocyte growth stimulated by BDL. Normal and BDL cholangiocytes expressed the biosynthetic pathway for and secrete progesterone. In vitro, 1) progesterone increased NRC proliferation; 2) cholangiocyte supernatants increased NRC proliferation, which was partially inhibited by preincubation with antiprogesterone; and 3) inhibition of progesterone steroidogenesis prevented NRC proliferation. In conclusion, progesterone may be an important autocrine/paracrine regulator of cholangiocyte proliferation.

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“…Virtually all living organisms display this characteristic pattern of protein synthesis to diverse stimuli including alcohols, free radicals, glucose starvation, heavy metals, hypoxia, fevers and inflammation. Thus, heat-shock proteins are now more commonly called stress proteins (2,3). This editorial will first present an overview of the biological roles of several classes of stress proteins and will consider the increasingly persuasive evidence of their potential clinical relevance in aging, cancer, cardiovascular disease and autoimmunity (3).…”

mentioning

confidence: 99%

Stress proteins: Is their application in clinical medicine on the horizon?

Benjamin

1993

Hepatology

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Steroid receptors and heat-shock proteins in patients with primary biliary cirrhosis

Cited by 3 publications

References 0 publications

Castration inhibits biliary proliferation induced by bile duct obstruction: novel role for the autocrine trophic effect of testosterone

Castration inhibits biliary proliferation induced by bile duct obstruction: novel role for the autocrine trophic effect of testosterone

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

Stress proteins: Is their application in clinical medicine on the horizon?

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