Molecular Characterization of Testicular Adrenal Rest Tumors in Congenital Adrenal Hyperplasia: Lesions With Both Adrenocortical and Leydig Cell Features

• Published in: The journal of clinical endocrinology and metabolism Vol. 100; no. 3; pp. E524 - E530
• Main Authors: Smeets, Evelien E. J. W, Span, Paul N, van Herwaarden, Antonius E, Wevers, Ron A, Hermus, Ad R. M. M, Sweep, Fred C. G. J, Claahsen-van der Grinten, Hedi L
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.03.2015; Copyright by The Endocrine Society
• Subjects: Adrenal Cortex - metabolism; Adrenal Cortex - pathology; Adrenal Hyperplasia, Congenital - complications; Adrenal Hyperplasia, Congenital - genetics; Adrenal Hyperplasia, Congenital - pathology; Adrenal Rest Tumor - complications; Adrenal Rest Tumor - genetics; Adrenal Rest Tumor - pathology; Adult; Gene Expression Regulation, Neoplastic; Humans; Leydig Cells - metabolism; Leydig Cells - pathology; Male; Testicular Neoplasms - complications; Testicular Neoplasms - genetics; Testicular Neoplasms - pathology; Transcriptome
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2014-2036

Context: Testicular adrenal rest tumors (TART) are one of the major long term complications in patients with congenital adrenal hyperplasia. Although several adrenal-like properties have been assigned to these benign lesions, the etiology has not been confirmed yet. Objective: The aim of this study was to describe TART in more detail by analyzing several (steroidogenic) characteristics that may be classified as adrenal cortex or Leydig cell specific. Methods: Gene expression analysis by qPCR was performed for 14 genes in TART tissue (n = 12) and compared with the expression in healthy control fibroblasts (nonsteroidogenic control). In addition, a comparison was made with the expression levels in testis tissue (n = 9) and adrenal tissue (n = 13). Results: Nearly all genes were highly expressed in TART tissue, including all genes that encode the key steroidogenic enzymes. TART expression levels are in the majority almost identical to those found in adrenal tissue. The expression of adrenal cortex specific genes (CYP11B1, CYP11B2, and MC2R) in both TART and adrenal tissue is approximately 1000–10 000 times higher compared to that in testes samples. In addition, the Leydig cell markers INSL3 and HSD17B3 were not only found in testes, but also in TART, both at significantly higher levels than in the adrenal (p < 0.01). Conclusion: Our study shows for the first time that TART have multiple steroidogenic properties, which include not only the expression of adrenal cortex but also of Leydig cell markers. Therefore, the origin of these tumors might be a more totipotent embryonic cell type.