SFEBES2022 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)
Normothermic machine liver perfusion as a tool to study human androgen metabolism
Amarah Anthony 1 , George Clarke 1,2 , Lina Schiffer 1 , Yiyu Fan 1 , James Hawley 3,1 , Fozia Shaheen 1 , Angus Hann 1,2 , Angela Taylor 1 , Simon Afford 1 & Wiebke Arlt 1
1University of Birmingham, Birmingham, United Kingdom; 2The Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; 3Wythenshawe Hospital, Manchester, United Kingdom
Background: In women, androgen excess is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Androgen precursors are released from the adrenal gland and converted to active androgens in peripheral tissues including adipose tissue. Although the liver plays a key role in all metabolic processes in the body, its involvement in androgen metabolism is yet to be explored. Here, we describe the investigation of androgen metabolism in human liver using normothermic machine liver perfusion.
Methods: A liver assist device was used to perfuse a human liver deemed unsuitable for transplantation. An established protocol validated for liver perfusion was used. After 2 hours, liver viability was confirmed by normalisation of the lactate concentration in perfusate and 200 nM of C13-labelled androstenedione was added. Perfusate samples were taken at regular intervals over 12 hours and steroid identification and quantification was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Results: Following the addition of C13-labelled androstenedione to the perfusate, we observed the majority of downstream metabolism occurring within the two subsequent hours, with quantifiable generation of 5a-dihydrotestosterone, androstanediol, androsterone and etiocholanolone. The overwhelming majority of androstenedione served as substrate for conversion to inactive downstream metabolites via the 5b-reductive pathway, whereas the conversion of androstenedione to active androgens only occurred in negligible amounts.
Conclusion: Normothermic machine liver perfusion is a highly suitable tool for ex vivo whole organ assessment of steroid metabolism in the human liver. We provided proof-of-principle of the use of this technique to investigate androgen metabolism in the liver and will utilise it to dissect the role of androgens in the development of conditions such as NAFLD.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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