Document Detail


Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms.
MedLine Citation:
PMID:  18511743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 mPRalpha) 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 mPRalpha. 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.
Authors:
Shannon Glaser; Sharon DeMorrow; Heather Francis; Yoshiyuki Ueno; Eugenio Gaudio; Shelley Vaculin; Julie Venter; Antonio Franchitto; Paolo Onori; Bradley Vaculin; Marco Marzioni; Candace Wise; Metaneeya Pilanthananond; Jennifer Savage; Lisa Pierce; Romina Mancinelli; Gianfranco Alpini
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-05-29
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  295     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-15     Completed Date:  2008-09-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G124-G136     Citation Subset:  IM    
Affiliation:
Department of Medicine, Scott & White Hospital and Texas A&M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA. sglaser@tamu.edu
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MeSH Terms
Descriptor/Qualifier:
3-Hydroxysteroid Dehydrogenases / genetics,  metabolism
Animals
Autocrine Communication / physiology*
Bile Ducts / cytology*,  drug effects*
Cell Proliferation / drug effects
Cytochrome P-450 Enzyme System / metabolism
Female
Gene Expression Regulation
Male
Paracrine Communication / physiology*
Phosphoproteins / genetics,  metabolism
Progesterone / pharmacology*
Rats
Rats, Inbred F344
Receptors, Progesterone / genetics,  metabolism
Sex Characteristics
Grant Support
ID/Acronym/Agency:
K01 DK-078532/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Phosphoproteins; 0/Receptors, Progesterone; 0/steroidogenic acute regulatory protein; 57-83-0/Progesterone; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.1.-/3-Hydroxysteroid Dehydrogenases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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