GATA transcription factors in testicular adrenal rest tumours

Endocrine Connections

Paul N Span¹  Lee B Smith²  Manon Engels³  Antonius E van Herwaarden⁴  Egbert Oosterwijk⁴  Nike M Stikkelbroeck⁵  Hedi L Claahsen-van der Grinten⁶  Christina A Hulsbergen-van de Kaa⁶  Monica A Marijnissen-van Zanten⁶  Joop J T M Heuvel⁷  Fred C G J Sweep⁷  Rod T Mitchell⁸ 

[1] Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud university medical center, Nijmegen, The Netherlands;Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands;Department of Paediatrics, Radboud Amalia Children’s Hospital, Radboud university medical center, Nijmegen, The Netherlands;Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands;Department of Urology, Radboud university medical center, Nijmegen, The Netherlands;Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud university medical center, Nijmegen, The Netherlands;MRC Centre for Reproductive Health, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK;Radiation Oncology, Radiotherapy and OncoImmunology Laboratory, RIMLS, Radboud university medical center, Nijmegen, The Netherlands;

关键词: congenital adrenal hyperplasia;    testicular adrenal rest tumour;    Leydig cell tumour;    GATA transcription factors;   

DOI  :  10.1530/EC-17-0215

来源: DOAJ

【 摘 要 】

Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro. Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.

【 授权许可】

Unknown