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Endocrine Abstracts (2021) 77 S2.1 | DOI: 10.1530/endoabs.77.S2.1

1Imperial College London, London, UK; 2Waters Corporation, Wilmslow, UK; 3University Hospital of Bari, Bari, Italy; 4Kings College London, London, UK


Liver X receptors (LXRs) are are ligand-dependent transcription factors, members of the nuclear receptor superfamily of transcription factors. In humans two LXR isoforms exist, LXRα (NR1H3) and LXRβ (NR1H2). LXRα is expressed predominantly in metabolically active tissues, while LXRβ is expressed in the majority of tissues. They have long been known to have critical roles in regulation of lipid metabolism, particularly cholesterol homeostasis; oxidised cholesterol metabolites are activating ligands for both LXRα and LXRβ.

In the testis, tightly regulated lipid metabolism is crucial for male fertility. LXRs are highly expressed in the testis but their role in regulating lipid homeostasis in this tissue is not fully understood. Lxrα/β double knockout male mice (Lxrα/β DKO) exhibit aberrations in lipid metabolism and are sterile by 7 months. We used integrated wide-platform studies and imaging methods to identify specific disrupted cellular lipids and novel candidate target genes in the testis. In addition to in vitro and genetic models, we developed an ex vivo human testicular model in which to model LXR pathways in human testis and identify LXR deregulation in human subfertility. We confirm for the first time that LXR pathways are active in human testis. Our results suggest the conventional roles of LXRs in cholesterol homeostasis are important in human testis, as previously described in mouse, and implicate LXRs in novel lipid pathways critical for male reproductive function.

Volume 77

Society for Endocrinology BES 2021

Edinburgh, United Kingdom
08 Nov 2021 - 10 Nov 2021

Society for Endocrinology 

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