ESPE Abstracts (2014) 82 FC1.6

Molecular Characterization of Testicular Adrenal Rest Tumours in Congenital Adrenal Hyperplasia; Lesions with both Adrenocortical and Leydig Cell Features

Evelien Smeetsa,b, Paul Spanc, Antonius van Herwaardenb, Ron Weversb, Fred Sweepb & Hedi Claahsen-van der Grintena

aDepartment of Paediatrics, Radboud University Medical Center, Nijmegen, The Netherlands; bDepartment of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; cDepartment of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands

Background: Characterization of testicular adrenal rest tumours (TART) are one of the major long-term complications in congenital adrenal hyperplasia (CAH) patients. Although several adrenal-like properties have been assigned to these benign lesions, the exact etiology has not been established yet.

Objective and Hypotheses: The aim of this study was to analyze several (steroidogenic) characteristics of TART tissue which may be classified as adrenal cortex or Leydig cell specific.

Method: Gene expression analysis by qPCR was performed for 15 genes in TART tissue (n=12) and compared with the expression in healthy control fibroblasts (non-steroidogenic control). The genes were subdivided in a common group for both adrenal cortex and Leydig cells (STAR, CYP11A1, CYP17A1, HSD3B2, and NR5A1), an adrenal cortex specific group (CYP21A2, CYP11B1, CYP11B2, AGTR2, and MC2R), a group with Leydig cell specific genes (LHCGR, INSL3, and HSD17B3) and a group with genes that mainly function in peripheral tissues (CYP19A1 and SRD5A1). In addition, a comparison was made with the expression levels in testes (n=9) and adrenal tissue (n=13).

Results: Nearly all genes were highly expressed in TART tissue, including all genes that encode the main steroidogenic enzymes. TART expression levels are in the majority almost identical to those found in adrenal tissue. The expression of adrenal cortex specific genes (CYP21A2, CYP11B1, CYP11B2, and MC2R) in both TART and adrenal tissue is ~1000–10 000 times higher than that in testes samples (P<0.05). In addition, expression of Leydig cell specific markers insulin-like 3, 17β-HSD3, and LH/hCG receptor was found in testes as well as in TART tissue, with significantly higher levels than the adrenal for INSL3 and HSD17B3 (P<0.01).

Conclusion: Our study shows for the first time that TART have multiple steroidogenic properties, which include not only the expression of specific adrenal cortex but also of Leydig cell markers. Therefore, the origin of these tumours might be a more totipotent embryonic cell type that may be stimulated by ACTH and LH.

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