Androgen steroidogenesis and functional effect in mucinous ovarian cancer cells, organoids and patient tumours

Lucy Beevors; Angela Taylor; Tejumola Olaoye; Suad Abdirahman; Olivia Craig; Wiebke Arlt; Paul Foster; Kylie Gorringe; Sudha Sundar

doi:10.1530/endoabs.117.P91

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Endocrine Abstracts (2026) 117 P91 | DOI: 10.1530/endoabs.117.P91

SFEBES2026 Poster Presentations Endocrine Cancer and Late Effects (12 abstracts)

Androgen steroidogenesis and functional effect in mucinous ovarian cancer cells, organoids and patient tumours

Lucy Beevors ¹ , Angela Taylor ¹ , Tejumola Olaoye ^2,3 , Suad Abdirahman ^4,5 , Olivia Craig ^4,5 , Wiebke Arlt ^6,7,1 , Paul Foster ^1,8 , Kylie Gorringe ^4,5 & Sudha Sundar ^3,9

Author affiliations

¹Metabolism and Systems Science, University of Birmingham, Birmingham, United Kingdom; ²Pan-Birmingham Gynaecological Cancer Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom; ³Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom; ⁴The Sir Peter MacCallum Dept of Oncology, University of Melbourne, Melbourne, Australia; ⁵Peter MacCallum Cancer Centre, Melbourne, Australia; ⁶MRC Laboratory of Medical Sciences, London, United Kingdom; ⁷Institute of Clinical Sciences, Imperial College London, London, United Kingdom; ⁸CEDAM, Birmingham, United Kingdom; ⁹Pan-Birmingham Gynaecological Cancer Centre, City Hospital, Birmingham, United Kingdom

Background: Ovarian cancer (OC) is the sixth most prevalent cancer and the deadliest gynaecological malignancy among UK females. Epithelial ovarian carcinoma (EOC) accounts for 90% of OC; mucinous ovarian carcinoma (MOC) is a rare EOC subtype, representing 3–5%, with advanced/ recurrent MOC carrying poor clinical outcomes. Previous work from our laboratory suggests steroidal metabolism in MOC patients is distinct from other EOC subtypes and healthy controls. Here, we investigate androgen metabolism and its consequences on MOC cell lines, organoids, and primary tumour tissue.

Methods: Steroidogenesis enzymes and receptor expression in MOC cells were assessed utilising two publicly available datasets and through RT-qPCR. Metabolism of androgenic steroids were investigated using LC-MS/MS in EOC cell lines, MOC organoid models and in human tumour tissue. Functional consequences of androgens on proliferation and migration in MOC cell lines were also investigated.

Results: The androgen metabolism enzymes SRD5A1/3 and HSD17B2/4 show similar RNA levels across cell lines. AKR1C3 expression is higher in MOC (2–10 TPM) than HGSOC (1–6 TPM). Androgen receptor (AR) and KLK4, an AR-response gene, RNA levels alter following androgen treatment. After 24-hours of testosterone treatment, synthesis of the less biologically active androstenedione was >6 times higher in MOC cell lines than HGSOC. Androstenedione was also the predominant metabolite of T conversion across MOC organoids (24nM after 6hrs, 40nM after 24hrs) and matched fresh patient tumour tissue (36nM after 24hrs). Androgens were also shown to negatively impact MOC proliferation compared to HGSOC.

Conclusion: Androgen metabolism is different between MOC and HGSOC cell lines. MOC cells demonstrated a preference towards synthesis of inactive androgens, which is consistent across 2D cells, organoids, and primary models. Furthermore, androgens may have a different functional effect in MOC compared to HGSOC.