Our research focuses on the molecular and epigenetic regulation of human sex development and androgen signalling in health and disease. A central aim of our work is to understand how steroid hormones and their signalling pathways shape reproductive development and contribute to human pathologies.
One major research area investigates androgen receptor (AR) function in differences of sex development (DSD), particularly androgen insensitivity syndrome (AIS). Although AIS is classically caused by mutations in the AR gene, more than half of clinically diagnosed individuals lack detectable AR coding mutations. We hypothesize that defects in AR cofactors and regulatory mechanisms contribute to these unexplained cases. Using functional assays in genital skin fibroblasts, we study tissue-specific AR activity and aim to identify novel molecular regulators involved in male sex differentiation. This work seeks to improve molecular diagnostics and advance our understanding of human sexual development.
A second focus examines the hormonal regulation of female reproductive development. Traditional models have viewed female sex development as a passive pathway, yet increasing evidence suggests that steroid hormones actively shape female genital differentiation and reproductive tissue function. We investigate hormone-responsive gene networks in female tissues and explore how dysregulation of these pathways contributes to disorders such as endometriosis.
Our third research area addresses the molecular basis of post-finasteride syndrome (PFS), a condition characterized by persistent sexual, psychological, and physical side effects following finasteride treatment. We investigate whether finasteride induces long-lasting epigenetic and transcriptomic alterations affecting androgen signalling pathways. By identifying molecular signatures associated with PFS, we aim to improve the understanding of this poorly characterized condition and its underlying mechanisms.
Selected publications
Stammberger B, Steinbach X, Hornig N. The persisting presence of absence in female sex development: a critical interdisciplinary reflection. Biol Sex Differ. 2026 Mar 25;17(1):71. doi: 10.1186/s13293-026-00848-2.
Comprehensive androgen-dependent transcriptome analysis in human genital tissue. Sivaprasad R, Händler K, Caliebe A, Spielmann M, Holterhus PM, Hornig NC. BMC Genomics. 2025 Nov 17;26(1):1047. doi: 10.1186/s12864-025-12212-6
Pozojevic J, Sivaprasad R, Laß J, Haarich F, Trinh J, Kakar N, Schulz K, Händler K, Verrijn Stuart AA, Giltay JC, van Gassen KL, Caliebe A, Holterhus PM, Spielmann M, Hornig NC. LINE1-mediated epigenetic repression of androgen receptor transcription causes androgen insensitivity syndrome. Sci Rep. 2024 Jul 15;14(1):16302. doi: 10.1038/s41598-024-65439-w. JIF: 3,8 h-Index: 315
Formin-mediated nuclear actin at androgen receptors promotes transcription. Julian Knerr, Ralf Werner, Carsten Schwan, Hong Wang, Peter Gebhardt, Helga Grötsch, Almuth Caliebe, Malte Spielmann, Paul-Martin Holterhus, Robert Grosse & Nadine C Hornig Nature. 2023 Mar 27. doi: 10.1038/s41586-023-05981-1
Molecular basis of androgen insensitivity syndromes. Hornig NC, Holterhus PM. Mol Cell Endocrinol. 2021 Mar 1;523:111146. doi: 10.1016/j.mce.2020.111146
Reduced Androgen Receptor Expression in Genital Skin Fibroblasts From Patients With 45,X/46,XY Mosaicism. Hornig NC, Demiri J, Rodens P, Murga Penas EM, Caliebe A, Eckstein AK, Schweikert HU, Audi L, Hiort O, Werner R, Kulle AE, Ammerpohl O, Holterhus PM. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4630-4638. doi: 10.1210/jc.2019-00108
Epigenetic Repression of Androgen Receptor Transcription in Mutation-Negative Androgen Insensitivity Syndrome (AIS Type II). Hornig NC, Rodens P, Dörr H, Hubner NC, Kulle AE, Schweikert HU, Welzel M, Bens S, Hiort O, Werner R, Gonzalves S, Eckstein AK, Cools M, Verrijn-Stuart A, Stunnenberg HG, Siebert R, Ammerpohl O, Holterhus PM. J Clin Endocrinol Metab. 2018 Dec 1;103(12):4617-4627. doi: 10.1210/jc.2018-00052
Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity. Hornig NC, Ukat M, Schweikert HU, Hiort O, Werner R, Drop SL, Cools M, Hughes IA, Audi L, Ahmed SF, Demiri J, Rodens P, Worch L, Wehner G, Kulle AE, Dunstheimer D, Müller-Roßberg E, Reinehr T, Hadidi AT, Eckstein AK, van der Horst C, Seif C, Siebert R, Ammerpohl O, Holterhus PM. J Clin Endocrinol Metab. 2016 Nov;101(11):4468-4477. doi: 10.1210/jc.2016-1990
A Recurrent Germline Mutation in the 5'UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation. Hornig NC, de Beaufort C, Denzer F, Cools M, Wabitsch M, Ukat M, Kulle AE, Schweikert HU, Werner R, Hiort O, Audi L, Siebert R, Ammerpohl O, Holterhus PM. PLoS One. 2016 Apr 25;11(4):e0154158. doi: 10.1371/journal.pone.0154158
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