IDSD2026 Poster Abstracts Poster Abstracts (93 abstracts)
Characterisation of leydig cells in individuals with genetic defects of androgen signalling
Mostafa Al-Sharkawi 1,2 , Letícia Moreno-Ambrozini 1 , Svenja Denker 3 , Yamil Maluje 3 , Anke Fähnrich 3 , Axel Künstner 3 , Kübra Kösem 1 , Verena-Wilbeth Sailer 4 , Florian Lenz 4 , Helena Fabbri-Scallet 5 , Gil Guerra-Júnior 6,7 , Olaf Hiort 1 , Hauke Busch 3 & Ralf Werner 1
1Division of Paediatric Endocrinology and Diabetology, Department of Paediatrics, University of Lübeck, 23562 Lübeck, Germany; 2Biochemical Genetics Department, Human Genetics and Genome Research Institute, 12622 Dokki, Cairo, Egypt; 3Medical Systems Biology Group, Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany; 4Institute of Pathology, University Hospital Schleswig-Holstein, Campus Lübeck, 23562 Lübeck Germany; 5Centre for Molecular Biology and Genetic Engineering, State University of Campinas, Campinas 13083-875, Brazil; 6Interdisciplinary Group for the Study of Sex Determination and Differentiation-GIEDDS, State University of Campinas, São Paulo, Brazil; 7Department of Paediatrics, Faculty of Medical Sciences, State University of Campinas, São Paulo, Brazil. Correspondence to: [email protected]
Background: Androgens play an important role in the proper differentiation of mammalian Leydig cells, including humans. Recently, we have shown that defective androgen signalling in adolescents and young adults with complete androgen insensitivity syndrome (CAIS) and CYP17A1-deficiency is associated with altered steroidogenesis, defective differentiation of Leydig cells and maintenance of foetal testicular features. Interestingly, in CAIS, HSD17B3 protein is expressed in Sertoli cells and not in Leydig cells, which is a feature known for the foetal mouse testis. Here, we further investigate the effects of defective androgen signalling on Leydig cells in complete and partial androgen insensitivity syndrome, (PAIS) and CYP17A1-deficiency.
Methods: Archived formalin-fixed, paraffin-embedded gonadal tissues from one adolescent and three young adults with CAIS, one child and one young adult with PAIS, and one young adult with CYP17A1-deficiency, one adolescent and two adult testicular tissues from Caucasians with no comorbidities were characterised by immunohistochemistry and single-molecule fluorescent in situ hybridisation (RNAscope).
Results: HSD17B3 mRNA was exclusively expressed in Sertoli cells in adolescent and young adult CAIS gonads and in the prepubertal PAIS gonad, a feature that have been known for the foetal mouse testis, and also shown by us recently in foetal, neonatal and prepubertal human testis. In the young adult PAIS gonad, however, the expression of HSD17B3 mRNA switched individually to some Leydig cells. HSD17B3-expressing Leydig cells showed higher expression of the mature/adult Leydig cell marker INSL3, while HSD17B3 non-expressing Leydig cells showed higher expression of the immature/foetal Leydig cell marker DLK1. Upregulation of HSD17B3 in Leydig cells in the young adult PAIS gonad was associated with its downregulation in the neighbouring Sertoli cells suggesting a coordinated, androgen-dependent progression of differentiation of both cell types.
Conclusions: Defective androgen signalling in CAIS and CYP17A1-deficiency is associated with an altered steroidogenesis and differentiation of Leydig cells, which is partially rescued in PAIS, suggesting that androgen signalling plays an essential role in Leydig cell development in humans. Further investigation of the coordinated development of Leydig and Sertoli cells in these conditions will be performed using spatial transcriptome analysis.
Volume 118
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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