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.
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Germany
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