Horm Metab Res 2024; 56(01): 38-44
DOI: 10.1055/a-2216-0269
Original Article: Endocrine Research

Quantitative Characterization of Ectopic Adrenal Gene Expression in Fetal Testes in 21-Hydroxylase Deficient Mice

Maximilian Weniger
1   Medizinische Klinik IV, LMU Klinikum München, Munich, Germany
Maria Mattes
1   Medizinische Klinik IV, LMU Klinikum München, Munich, Germany
Thomas G.P. Grünewald
2   Max Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, LMU Klinikum München, Munich, Germany
Katrin Köhler
3   Pediatric Endocrinology, Children's Hospital, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Angela Hübner
3   Pediatric Endocrinology, Children's Hospital, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
1   Medizinische Klinik IV, LMU Klinikum München, Munich, Germany
4   Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, UniversitätsSpital Zürich, Zürich, Switzerland
Nicole Reisch
1   Medizinische Klinik IV, LMU Klinikum München, Munich, Germany
› Author Affiliations
Fundings Deutsche Forschungsgemeinschaft — http://dx.doi.org/10.13039/501100001659; 314061271-TRR205 Else Kröner Fresenius Stifstung — 2011-EKMS2.1 Deutsche Krebshilfe — http://dx.doi.org/10.13039/501100005972; German Cancer Aid, DKH-70112257


Testicular adrenal rest tumors (TART) are a frequent and fertility impairing long-term complication in males with classic congenital adrenal hyperplasia. Due to lack of clear experimental data on their origin, they are hypothesized to be derived from ectopic adrenocortical cells within testicular tissue mainly growing upon stimulation by chronically elevated levels of adrenocorticotropin (ACTH). Alternatively, a more totipotent embryological origin has been discussed as the potential source of these tumors. The aim of this study was to quantify alterations of ectopic expression of adrenocortical genes (CYP11B1, CYP11B2, CYP21, MC2R) and the Leydig cell specific marker (INSL3) in testicular tissue of fetal 21-hydroxylase deficient (21OHD) mice. Timed-pregnancy studies were performed using H-2aw18 (aw18)-mice. Testes and adrenals of E15.5 and E18.5 mouse fetuses were used for real-time PCR and immunohistochemistry. Gene expression levels were analyzed for genotype-dependent alterations and compared with immunohistochemistry. While enzymes of steroidogenesis showed a significant increased expression in adrenals of 21OHD mice at both E15.5 and E18.5 compared to wild-type (WT) mice, expression levels were unaltered in testes of 21OHD mice. When compared to WT adrenals a significant increase of INSL3 expression in adrenals of 21OHD mice at E15.5 and E18.5 was detected. Cells with adrenocortical properties in mice fetal testis differ from in situ adrenocortical cells in gene expression and growth at E15.5 and E18.5. These findings suggest that the different local regulation and different local niche in adrenals and testes influence growth of aberrant adrenal cells.

Supplementary Material

Publication History

Received: 26 June 2023

Accepted after revision: 21 November 2023

Article published online:
03 January 2024

© 2024. Thieme. All rights reserved.

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