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 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.
Highlights
Congenital adrenal hyperplasia (CAH) is a genetic disorder in which adrenocortical steroid synthesis is impaired due to a deficiency in particular steroidogenic enzymes, most often steroid 21-hydroxylase (CYP21A2)
To test whether expression of GATA1, GATA3, GATA4 and GATA6 is a marker of different tissues or disease states, qPCR was performed (Fig. 1)
To the best of our knowledge, this is the first description of GATA transcription factors in human testicular adrenal rest tumours (TARTs)
Summary
Congenital adrenal hyperplasia (CAH) is a genetic disorder in which adrenocortical steroid synthesis is impaired due to a deficiency in particular steroidogenic enzymes, most often steroid 21-hydroxylase (CYP21A2). A wide range of the male CAH patients from 12.5% up to 94% are reported to develop testicular adrenal rest tumours (TARTs), which are an important cause of infertility (1, 2). TARTs are benign tumours with steroidogenic characteristics, located near the mediastinum testis (1, 3). TARTs were originally thought to arise from adrenal rest cells, based on the presence of adrenal characteristics, such as expression of adrenal enzymes and receptors (4, 5). Recently we described testicular characteristics of TARTs (6). This has shifted the hypothesis toward a more pluripotent steroidogenic cell type as the origin of TARTs (6), possibly from cells originating in the urogenital ridge or adrenogonadal primordium
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