Endocrine Abstracts (2017) 49 GP10 | DOI: 10.1530/endoabs.49.GP10

Expression of GATA transcription factors and their role in the aetiology of Testicular Adrenal Rest Tumours

Manon Engels1,2, Paul Span3, Monica Marijnissen-van Zanten4, Teun van Herwaarden2, Christina Hulsbergen-van de Kaa4, Rod Mitchell6, Lee Smith6, Nike Stikkelbroeck5, Fred Sweep2 & Hedi Claahsen-van der Grinten1


1Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands; 2Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; 3Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands; 4Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; 5Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; 6Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.


Background: Recently, GATA transcription factors have been linked to the development of Testicular Adrenal Rest Tumours (TART), benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia (CAH). The objective of this study is to determine GATA expression in TART and other steroidogenic tissues, examining their discriminative potential and their possible role in the aetiology of TART.

Methods: GATA1-6 expression was determined in TART, Leydig cell tumour (LCT), adult testis, adult adrenal, foetal testis, and foetal adrenal tissues. In addition, GATA expression was measured in Hs181.tes cells after induction with dibutyryl cAMP (dbcAMP).

Results: In TART, testis-like GATA4 gene expression, but higher compared to adult adrenal, was found. In contrast, GATA3 and GATA6 expression in TART is similar to adrenal, but higher compared to adult testis or LCT. GATA3 and GATA6 could discriminate between TART and testis (AUC of 0.982 and 0.920, respectively). ACTH is a potential stimulator of TART differentiation in CAH. Stimulation of the Hs181.tes cell line with 0.1 mM dbcAMP for 4 hours increased gene expression of both GATA3 and GATA6.

Conclusion: Gene expression of GATA transcription factors in TART shows both testicular and adrenal characteristics. Additionally, GATA3 and GATA6 mRNA levels can help discriminate TART from LCT. Furthermore, we found that dbcAMP can induce GATA3 and GATA6 gene expression, which might indicate that ACTH can stimulate testis cells to become more adrenal like and eventually TART cells. To confirm this, we are pending on the results of stimulation experiments with dbcAMP or ACTH in ACTH-responsive H295RA cells.