GATA transcription factors in testicular adrenal rest tumours

Manon Engels, Paul N Span, Rod T Mitchell, Joop J T M Heuvel, Monica A Marijnissen-van Zanten, Antonius Eduard van Herwaarden, Christina A Hulsbergen-van de Kaa, Egbert Oosterwijk, Nike M Stikkelbroeck, Lee B Smith, Fred C G J Sweep, Hedi L Claahsen-van der Grinten

Research output: Contribution to journalArticlepeer-review

Abstract

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 expression 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 mRNA 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 4h stimulated GATA3, GATA4, and GATA6 expression 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.

Original languageEnglish
JournalEndocrine connections
Early online date16 Oct 2017
DOIs
Publication statusE-pub ahead of print - 16 Oct 2017

Keywords

  • Journal Article

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