GATA transcription factors in testicular adrenal rest tumours

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.

Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues

“…Compared to adult adrenal tissue, TART highly overexpressed testis-specific DEFB119, PRM2, and GATA4 ( Figure 3B). GATA4 expression in TART has been reported previously by our group (20). Previous studies proposed the expression of the testis-specific Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) in TART (16,21).…”

“…The identity and functional characteristics of TART are incompletely understood. Previous research focusing on the characterization of TART reported both adrenal-(26-28) and testis-specific (20,27) characteristics. However, these studies focused only on a subset of candidate markers.…”

Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth

“…GATA4 is well known for its central role in embryogenesis [7], and in myocardial differentiation and function [8]. Besides, this protein is thought to be necessary for testicular development [9]. Mutations in this gene have been associated with various diseases.…”

Editorial Comment to Testicular adrenal rest tumor without congenital adrenal hyperplasia: A rare case

“…They also might have a multiple primordial origin from pluripotent cells in the original locations. 4 These rests might be present in 50% of newborns, but most of them become atrophic by the time they reach adulthood.…”

“…It is accepted that adrenal rests were due to mechanical separation and displacement of portions of cortical tissue during migration and descent of the sex glands in male embryonic development. They also might have a multiple primordial origin from pluripotent cells in the original locations . These rests might be present in 50% of newborns, but most of them become atrophic by the time they reach adulthood.…”