Evaluation of Ex Vivo Adrenocorticotropic Hormone Responsiveness of Human Fetal Testis

Author:

Schröder Mariska A M123ORCID,Greenald David3,Lodewijk Renate2,van Herwaarden Antonius E2,Span Paul N4ORCID,Sweep Fred C G J2,Mitchell Rod T3,Claahsen-van der Grinten Hedi L1ORCID

Affiliation:

1. Department of Pediatrics, Radboud Amalia Children's Hospital, Radboud University Medical Center , 6500 HB Nijmegen , The Netherlands

2. Department of Laboratory Medicine, Radboudumc Graduate School, Radboud University Medical Center , 6500 HB Nijmegen , The Netherlands

3. MRC Centre for Reproductive Health, Institute for Regeneration and Repair, The University of Edinburgh, and the Royal Hospital for Children and Young People , Edinburgh EH16 4TJ , UK

4. Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboudumc Graduate School, Radboud University Medical Center , 6500 HB Nijmegen , The Netherlands

Abstract

Abstract 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.

Funder

Wellcome Trust

Publisher

The Endocrine Society

Subject

Endocrinology

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