TY - JOUR
T1 - Evaluation of Ex Vivo Adrenocorticotropic Hormone Responsiveness of Human Fetal Testis
AU - Schröder, Mariska A M
AU - Greenald, David
AU - Lodewijk, Renate
AU - van Herwaarden, Antonius E
AU - Span, Paul N
AU - Sweep, Fred C G J
AU - Mitchell, Rod T
AU - Claahsen-van der Grinten, Hedi L
N1 - Funding Information:
The human fetal material was provided by the Joint MRC/Wellcome Trust (Grant # MR/006237/1) Human Developmental Biology Resource (http://www.hdbr.org). The project was supported by the ESE Short-Term Fellowship grant to MAMS.
Funding Information:
The human fetal material was provided by the Joint MRC/Wellcome Trust (Grant # MR/006237/1) Human Developmental Biology Resource ( http://www.hdbr.org ). The project was supported by the ESE Short-Term Fellowship grant to MAMS.
Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Testicular adrenal rest tumors (TARTs), commonly occurring in males with congenital adrenal hyperplasia, may arise from chronic stimulation of adrenocorticotropic hormone (ACTH)-sensitive cells in the testes. It is not yet established whether the human fetal testis (HFT) is responsive to ACTH. To investigate this, we cultured HFT tissue with and without ACTH for up to 5 days, and quantified adrenal steroid hormones and expression of adrenal steroidogenic enzymes. Fetal testis and adrenal tissue produced high levels of testosterone and cortisol, respectively, indicating viability. In contrast to fetal adrenal tissues, the expression of ACTH receptor MC2R was either absent or expressed at extremely low levels in ex vivo HFT tissue and no clear response to ACTH in gene expression or steroid hormone production was observed. Altogether, this study suggests that the HFT is unresponsive to ACTH, which would indicate that a TART does not arise from fetal testicular cells chronically exposed to ACTH in utero.
AB - Testicular adrenal rest tumors (TARTs), commonly occurring in males with congenital adrenal hyperplasia, may arise from chronic stimulation of adrenocorticotropic hormone (ACTH)-sensitive cells in the testes. It is not yet established whether the human fetal testis (HFT) is responsive to ACTH. To investigate this, we cultured HFT tissue with and without ACTH for up to 5 days, and quantified adrenal steroid hormones and expression of adrenal steroidogenic enzymes. Fetal testis and adrenal tissue produced high levels of testosterone and cortisol, respectively, indicating viability. In contrast to fetal adrenal tissues, the expression of ACTH receptor MC2R was either absent or expressed at extremely low levels in ex vivo HFT tissue and no clear response to ACTH in gene expression or steroid hormone production was observed. Altogether, this study suggests that the HFT is unresponsive to ACTH, which would indicate that a TART does not arise from fetal testicular cells chronically exposed to ACTH in utero.
KW - adrenocorticotropic hormone
KW - congenital adrenal hyperplasia
KW - human fetal testis
KW - testicular adrenal rest tumors
U2 - 10.1210/endocr/bqad165
DO - 10.1210/endocr/bqad165
M3 - Article
C2 - 37935047
SN - 0013-7227
VL - 164
JO - Endocrinology
JF - Endocrinology
IS - 12
M1 - bqad165
ER -