hrp0089p2-p368 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P2 | ESPE2018

A Case of Gonadal Dysgenesis Due to a Novel Homozygous Mutation in NR5A2 Gene

Denzer Friederike , Denzer Christian , Hornig Nadine , Holterhus Paul-Martin , Hiort Olaf , Wabitsch Martin

Background: Steroidogenic factor (SF1, NR5A2) regulates multiple genes known to be involved in gonadal development, adrenal development, steroidogenesis, and gonadotroph development. Heterozygous mutations in the NR5A1 gene have been described in association with mild to severe gonadal dysgenesis with or without adrenal failure. Homozygous mutations are rare and have also been described in association with gonadal dysgenesis with or without adrenal failure.<p class="abstex...

hrp0094p1-9 | Adrenal A | ESPE2021

Backdoor Pathway hormones and 11-oxygenated Androgens are elevated in Patients with 21-hydroxylase deficiency

Kulle Alexandra , Lamprecht Tabea , Pinto Francisca , Wulf Kristina , Hornig Nadine , Reinehr Thomas , Holterhus Paul-Martin ,

Background: Patients with 21-Hydroxylase deficiency (21OHD) present increased levels of cytochrome P450 21-hydroxylase substrates, like progesterone and 17α-hydroxyprogesterone. Previous studies could show that these hormones are involved in the production of androgens via the backdoor pathway. As a second source of androgens, 11-oxyandrogens derived from the human adrenal glands are recognized as being major androgens. Specifically, 11-oxyandrogens ...

hrp0089p1-p217 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P1 | ESPE2018

Reduced Androgen Receptor Expression in Patients with 45,X/46,XY Mosaicism

Hornig Nadine , Demiri Jeta , Murga Eva , Caliebe Almuth , Schweikert Hans-Udo , Audi Laura , Werner Ralf , Hiort Olaf , Holterhus Paul-Martin

Background: Individuals born with a 45,X/46,XY karyotype can present with diverging phenotypes from normal male, Turner-like to ambiguous genitalia, the latter classically being called mixed gonadal dysgenesis. No correlation between phenotype and degree of mosaicisms in the karyotype could be ascertained so far, making clinical management of these patients difficult.Objective: To understand, if androgen action through the androgen receptor (AR) is compr...

hrp0095p1-583 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Androgen receptor activity in genital skin fibroblasts in response to dihydrotestosterone, testosterone and androstenedione using the APOD assay

Große-Schute Lea , Kulle Alexandra , Werner Ralf , Hiort Olaf , Drop Stenvert , Schweikert Hans-Udo , Holterhus Paul-Martin , Hornig Nadine

Introduction: Androgens are essential for the development of male sex characteristics. Testosterone (T) production from androstenedione (A) by the Hydroxysteroid 17-Beta Dehydrogenase 3 (HSD17B3) in gonadal Leydig cells triggers the differentiation of the Wolffian ducts into epididymis, vas deferens, seminal vesicles and the prostate. Shortly after, the virilisation of the external male genitalia starts through the conversion of T into dihydrotestosterone (DHT...

hrp0082p2-d1-264 | Adrenals &amp; HP Axis | ESPE2014

LC–MSMS Profiling of Plasma Steroids in Different Types of Congenital Adrenal Hyperplasia

Kulle Alexandra E. , Reinehr Thomas , Akkurt Halit Ilker , Commentz Christian , Heger Sabine , Simic-Schleicher Gunter , Welzel Maik , Hornig Nadine C. , Holterhus Paul-Martin

Background: Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders which lead to impairment of steroid biosynthesis in the adrenals and gonads. 21-hydroxylase deficiency (21OHD) is the most common form of CAH (95%), followed by 11β-hydroxylase deficiency (11OHD) and 3β-dehydrogenase steroid dehydrogenase type 2 deficiency (3bHSD2). LC–MSMS based steroid analysis has become an increasingly important method for steroid analyses i...

hrp0084fc6.1 | Gonads &amp; DSD | ESPE2015

Correlation of AR Expression and AR Transcriptional Activity in Cultured Human Genital Fibroblasts

Hornig Nadine , Rodens Pascal , Ukat Martin , Demiri Jeta , Eckstein Anne Katrin , van der Horst Christof , Seif Christoph , Ammerpohl Ole , Holterhus Paul-Martin

Background: The androgen receptor (AR) is essential for the development of primary and secondary male characteristics and is activated by its ligand dihydrotestosterone (DHT). Reduced AR activity can cause undervirilization and infertility. We recently developed an assay to test AR function as a ligand-dependent transcriptional activator in human genital skin fibroblasts (GF). So far it is unclear, if AR expression levels correlate with AR function in the male external genital...

hrp0089rfc1.6 | Adrenals &amp; HPA Axis | ESPE2018

A Laboratory Harmonization Strategy for Steroid Hormone Profiling by MoM-Transformed, Normalized Reference Ranges Independent of Age, Sex and Units

Kulle Alexandra E , Zalas Dominika , Reinehr Thomas , Niedziela Marek , Borzikowsky Christoph , Pinto Francisca , Baumann Juliane , Flader Maciej , Simic-Schleicher Gunter , Akkurt Halit Ilker , Heger Sabine , Hornig Nadine , Holterhus Paul-Martin

Background/aims: The high complexity of Pediatric reference ranges across age, sex and units impairs clinical application and comparability of steroid hormone data, e.g., in CAHs. We developed a Multiples-of-Median (MoM) normalization tool to overcome this major drawback in Pediatric Endocrinology.Methods: LC–MS/MS data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to >16 years) from two previous datasets we...

hrp0082fc6.2 | Gonads &amp; DSD | ESPE2014

Next Generation Sequencing of the Androgen Receptor Gene in Patients With Androgen Insensitivity Syndrome and Controls

Hornig Nadine , Schweikert Hans-Udo , Ukat Martin , Kulle Alexandra , Welzel Maik , Wehner Gaby , Werner Ralf , Hiort Olaf , Drop Stenvert , Cools Martine , de Beaufort Carine , Siebert Reiner , Ammerpohl Ole , Holterhus Paul-Martin

Background: In a large fraction of patients with clinically presumed Androgen Insensitivity Syndrome, no mutation of the Androgen Receptor gene can be detected. However, established Sanger sequencing techniques of the AR gene are often limited to the coding region.Objective and Hypotheses: To set up a next generation sequencing (NGS) approach of the entire AR locus (including UTRs, exons, introns, up- and downstream regions) for a comprehensive ...

hrp0094p1-150 | Sex Endocrinology and Gonads B | ESPE2021

Androgen insensitivity without an androgen receptor mutation: results from a large cohort study

Hornig Nadine , Kulle Alexandra , Dombrowsky Gregor , Ammerpohl Ole , Caliebe Almuth , Schweikert Hans-Udo , Audi Laura , Cools Martin , Hannema Sabine , Stuart Annemarie Verrijn , Werner Ralf , Hiort Olaf , Holterhus Paul-Martin ,

Introduction: Androgen insensitivity syndrome (AIS) is a 46,XY difference of sex development (DSD) classically caused by mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, in over 50% of individuals with clinical AIS no AR coding gene mutation can be found. We previously established an assay (apolipoprotein D (APOD) assay) that measures androgen dependent AR-activity in genital skin fibroblasts (GFs). Using this assay we identified a gro...