Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2020) 70 AEP379 | DOI: 10.1530/endoabs.70.AEP379

ECE2020 Audio ePoster Presentations Diabetes, Obesity, Metabolism and Nutrition (285 abstracts)

TGFβ1 downregulates hepatic SHBG production by decreasing HNF-4α levels via SMAD and STAT3 pathways

Laura Brianso-LLort , Lidia Fuertes-Rioja , Cristina Hernandez , Rafael Simo & David Martinez


Vall d’Hebron Research Institue, Diabetes and Metabolism, Barcelona, Spain


Low plasmasex hormone-binding globulin (SHBG) levels are present in fatty liver disease, which represents a spectrum of diseases ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. We are interested in studying the molecular mechanisms by which plasma SHBG levels are reduced in fatty liver disease. In this regard, we have previously shown that fat accumulation in the liver reduces SHBG production by reducing hepatic nuclear factor 4 alpha (HNF-4α), a main regulator of SHBG expression. Transforming growth factor β1 (TGFβ1) plays an important role in the pathogenesis of liver fibrosis, being involved in activation of hepatic stellate cells, stimulation of collagen gene transcription, and modulation of matrix metalloproteinase expression. The aim of the present studywas to evaluate the role of TGFβ1 in regulating hepatic SHBG production. For this purpose, in vitro and in vivo studies were performed using human HepG2 cells and human SHBGtransgenic mice. Our results showed that TGFβ1 treatment reduces SHBG production (mRNA and protein) in HepG2 cells. In addition, human SHBG transgenic mice treated withTGFβ1 showed a significant reduction SHBG expression as well as in plasma SHBG levels. Mechanistically TGFβ1 downregulates HNF-4α levels via SMAD and STAT3 pathways through TGFβ1 receptor I. Taking together, we found for the first time that TGFβ1 regulates hepatic SHBG production. These results may explain why patients with fibrotic livers show low plasma SHBG levels.

Volume 70

22nd European Congress of Endocrinology

Online
05 Sep 2020 - 09 Sep 2020

European Society of Endocrinology 

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