Gonadotropin-releasing hormone stimulates biliary proliferation by paracrine/autocrine mechanisms

The American Journal of Pathology
Debolina RayShannon Glaser

Abstract

During cholestatic liver disease, there is dysregulation in the balance between biliary growth and loss in bile duct-ligated (BDL) rats modulated by neuroendocrine peptides via autocrine/paracrine pathways. Gonadotropin-releasing hormone (GnRH) is a trophic peptide hormone that modulates reproductive function and proliferation in many cell types. We evaluated the autocrine role of GnRH in the regulation of cholangiocyte proliferation. The expression of GnRH receptors was assessed in a normal mouse cholangiocyte cell line (NMC), sham, and BDL rats. The effect of GnRH administration was evaluated in normal rats and in NMC. GnRH-induced biliary proliferation was evaluated by changes in intrahepatic bile duct mass and the expression of proliferation and function markers. The expression and secretion of GnRH in NMC and isolated cholangiocytes was assessed. GnRH receptor subtypes GnRHR1 and GnRHR2 were expressed in cholangiocytes. Treatment with GnRH increased intrahepatic bile duct mass as well as proliferation and function markers in cholangiocytes. Transient knockdown and pharmacologic inhibition of GnRHR1 in NMC decreased proliferation. BDL cholangiocytes had increased expression of GnRH compared with normal rats, accompanied by ...Continue Reading

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Citations

Aug 15, 2015·Cellular and Molecular Gastroenterology and Hepatology·Luca MaroniGianfranco Alpini
Jun 27, 2017·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Keisaku SatoGianfranco Alpini
Oct 3, 2018·International Journal of Molecular Sciences·Debora Maria GiordanoMarco Marzioni
Aug 17, 2018·The Journal of Clinical Endocrinology and Metabolism·Emma NilssonElisabet Stener-Victorin
Aug 16, 2018·F1000Research·Marinda ScrushyShannon Glaser
Jul 29, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Matthew McMillinGianfranco Alpini
Jul 17, 2019·Current Medicinal Chemistry·Haralambos TzoupisTheodore Tselios
Jun 22, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Sophie E AapkesJoost P H Drenth
Jul 15, 2016·Gene Expression·Chad HallGianfranco Alpini

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