Paul Martin Holterhus

Summary

Country: Germany

Publications

  1. doi request reprint Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia
    Maik Welzel
    Division of Pediatric Endocrinology, Department of Pediatrics, Christian Albrechts Universitat zu Kiel, 24105 Kiel, Germany
    J Clin Endocrinol Metab 93:1418-25. 2008
  2. pmc Differential gene-expression patterns in genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome: evidence for early programming involving the androgen receptor
    Paul Martin Holterhus
    Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Genome Biol 4:R37. 2003
  3. ncbi request reprint Anabolic steroids, testosterone-precursors and virilizing androgens induce distinct activation profiles of androgen responsive promoter constructs
    P M Holterhus
    Department of Pediatrics, Medical University of Lubeck, Germany
    J Steroid Biochem Mol Biol 82:269-75. 2002
  4. pmc Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome
    Paul Martin Holterhus
    Department of Pediatrics, University Hospital Schleswig Holstein, Campus Kiel, Schwanenweg 20, Kiel, Germany
    BMC Genomics 8:376. 2007
  5. pmc Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
    Paul Martin Holterhus
    Department of Pediatrics, Christian Albrechts University of Kiel, Germany
    BMC Genomics 10:292. 2009
  6. ncbi request reprint Analyzing the functional and structural consequences of two point mutations (P94L and A368D) in the CYP11B1 gene causing congenital adrenal hyperplasia resulting from 11-hydroxylase deficiency
    Nils Krone
    Division of Pediatric Endocrinology, Department of Pediatrics, Christian Albrechts Universitat zu Kiel, Universitätsklinikum Schleswig Holstein Campus Kiel, Schwanenweg 20, D 24105 Kiel, Germany
    J Clin Endocrinol Metab 91:2682-8. 2006
  7. doi request reprint Congenital lipoid adrenal hyperplasia: functional characterization of three novel mutations in the STAR gene
    Susanne Bens
    Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Schleswig Holstein, Schwanenweg 20, D 24105 Kiel, Germany
    J Clin Endocrinol Metab 95:1301-8. 2010
  8. doi request reprint Transcriptional response of peripheral blood mononuclear cells to recombinant human growth hormone in a routine four-days IGF-I generation test
    Maik Welzel
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Christian Albrechts University, Kiel, Germany
    Growth Horm IGF Res 21:336-42. 2011
  9. ncbi request reprint Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males
    Susanne Thiele
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Lubeck, Lubeck, Germany
    Eur J Endocrinol 152:875-80. 2005
  10. doi request reprint Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome
    Mahesh Appari
    Department of Pediatrics, University Hospital Schleswig Holstein, Christian Albrechts University of Kiel, Germany
    J Mol Med (Berl) 87:623-32. 2009

Collaborators

Detail Information

Publications39

  1. doi request reprint Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia
    Maik Welzel
    Division of Pediatric Endocrinology, Department of Pediatrics, Christian Albrechts Universitat zu Kiel, 24105 Kiel, Germany
    J Clin Endocrinol Metab 93:1418-25. 2008
    ..Most mutations are located within domains regarded crucial for enzyme function. The function of the C terminus of the 3beta-HSD protein is not known...
  2. pmc Differential gene-expression patterns in genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome: evidence for early programming involving the androgen receptor
    Paul Martin Holterhus
    Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Genome Biol 4:R37. 2003
    ....
  3. ncbi request reprint Anabolic steroids, testosterone-precursors and virilizing androgens induce distinct activation profiles of androgen responsive promoter constructs
    P M Holterhus
    Department of Pediatrics, Medical University of Lubeck, Germany
    J Steroid Biochem Mol Biol 82:269-75. 2002
    ..We conclude that steroid-specific differences in gene transcription profiles due to androgen receptor activation could contribute to differences in biological actions of androgens...
  4. pmc Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome
    Paul Martin Holterhus
    Department of Pediatrics, University Hospital Schleswig Holstein, Campus Kiel, Schwanenweg 20, Kiel, Germany
    BMC Genomics 8:376. 2007
    ....
  5. pmc Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
    Paul Martin Holterhus
    Department of Pediatrics, Christian Albrechts University of Kiel, Germany
    BMC Genomics 10:292. 2009
    ..g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46, XY-males and 46, XX-females...
  6. ncbi request reprint Analyzing the functional and structural consequences of two point mutations (P94L and A368D) in the CYP11B1 gene causing congenital adrenal hyperplasia resulting from 11-hydroxylase deficiency
    Nils Krone
    Division of Pediatric Endocrinology, Department of Pediatrics, Christian Albrechts Universitat zu Kiel, Universitätsklinikum Schleswig Holstein Campus Kiel, Schwanenweg 20, D 24105 Kiel, Germany
    J Clin Endocrinol Metab 91:2682-8. 2006
    ..Congenital adrenal hyperplasia is a group of autosomal recessive inherited disorders of steroidogenesis. The deficiency of steroid 11-hydroxylase (CYP11B1) resulting from mutations in the CYP11B1 gene is the second most frequent cause...
  7. doi request reprint Congenital lipoid adrenal hyperplasia: functional characterization of three novel mutations in the STAR gene
    Susanne Bens
    Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Schleswig Holstein, Schwanenweg 20, D 24105 Kiel, Germany
    J Clin Endocrinol Metab 95:1301-8. 2010
    ..We speculate that the substitution of hydrophilic glutamine with basic arginine at the surface of the molecule may accelerate cholesterol transfer...
  8. doi request reprint Transcriptional response of peripheral blood mononuclear cells to recombinant human growth hormone in a routine four-days IGF-I generation test
    Maik Welzel
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Christian Albrechts University, Kiel, Germany
    Growth Horm IGF Res 21:336-42. 2011
    ..Genome-wide transcriptional changes in peripheral blood mononuclear cells (PBMC) have been widely used as functional readout for different pharmacological stimuli...
  9. ncbi request reprint Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males
    Susanne Thiele
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Lubeck, Lubeck, Germany
    Eur J Endocrinol 152:875-80. 2005
    ..We investigated whether 5RI is transcribed in normal male genital skin fibroblasts (GSFs) and if the transcription is regulated by age or by androgens themselves...
  10. doi request reprint Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome
    Mahesh Appari
    Department of Pediatrics, University Hospital Schleswig Holstein, Christian Albrechts University of Kiel, Germany
    J Mol Med (Berl) 87:623-32. 2009
    ..Therefore, qRT-PCR of APOD messenger RNA transcription in primary cultures of labioscrotal skin fibroblasts is a promising tool for assessing AR function, potentially allowing a function-based diagnostic evaluation of AIS in the future...
  11. ncbi request reprint A novel homozygous disruptive mutation in the SRD5A2-gene in a partially virilized patient with 5alpha-reductase deficiency
    Olaf Hiort
    Department of Pediatrics, Medical University of Lubeck, Lubeck, Germany
    Int J Androl 25:55-8. 2002
    ..This case demonstrates that even despite a complete loss of function of 5alpha-reductase type 2, marked virilization is possible, most likely the result of a testosterone (T) effect during foetal life...
  12. pmc Predicting the optimal basal insulin infusion pattern in children and adolescents on insulin pumps
    Paul Martin Holterhus
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Christian Albrechts University of Kiel, University Hospital of Schleswig Holstein, Campus Kiel, Kiel, Germany
    Diabetes Care 36:1507-11. 2013
    ..We aimed at developing and cross-validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy (CSII)...
  13. ncbi request reprint Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure
    Olaf Hiort
    Department of Pediatrics, Division of Pediatric Endocrinology, University Hospital Schleswig Holstein, Campus Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany
    J Clin Endocrinol Metab 90:538-41. 2005
    ..The possibility of P450scc-independent pathways of steroid synthesis in addition to the current concept of luteoplacental shift of progesterone synthesis in humans has to be questioned...
  14. doi request reprint Implementation of a liquid chromatography tandem mass spectrometry assay for eight adrenal C-21 steroids and pediatric reference data
    Alexandra E Kulle
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Schleswig Holstein, Christian Albrechts University Kiel, Kiel, Germany
    Horm Res Paediatr 79:22-31. 2013
    ....
  15. ncbi request reprint The basis of gender assignment in disorders of somatosexual differentiation
    Olaf Hiort
    Clinical Research Group Intersex From Gene to Gender KFO 111, Department of Paediatrics, University of Lubeck, Lubeck, Germany
    Horm Res 64:18-22. 2005
    ..Premature decisions leading to irreversible interventions before an accurate diagnosis has been established must be avoided...
  16. ncbi request reprint Transactivation properties of wild-type and mutant androgen receptors in transiently transfected primary human fibroblasts
    P M Holterhus
    Department of Pediatrics, University Hospital Schleswig Holstein, Campus Lubeck, Lubeck, Germany
    Horm Res 63:152-8. 2005
    ....
  17. ncbi request reprint Phenotypic diversity and testosterone-induced normalization of mutant L712F androgen receptor function in a kindred with androgen insensitivity
    P M Holterhus
    Department of Pediatrics, Medical University of Lubeck, Germany
    J Clin Endocrinol Metab 85:3245-50. 2000
    ....
  18. ncbi request reprint Expression of two functionally different androgen receptors in a patient with androgen insensitivity
    P M Holterhus
    Department of Paediatrics, Medical University of Lubeck, Germany
    Eur J Pediatr 158:702-6. 1999
    ..It underlines the importance of particular notice on somatic mosaicism in all androgen insensitivity syndrome patients carrying de novo mutations of the androgen receptor gene...
  19. ncbi request reprint The molecular basis of male sexual differentiation
    O Hiort
    Department of Paediatrics, Medical University of Lubeck, Lubeck, Germany
    Eur J Endocrinol 142:101-10. 2000
    ..Disruption of these genetic events leads to sexual dimorphism involving external and internal genitalia, and may also interfere with the development of other organs...
  20. ncbi request reprint Androgen insensitivity and male infertility
    O Hiort
    Department of Pediatrics, University Hospital of Lübeck, Germany
    Int J Androl 26:16-20. 2003
    ..However, the molecular mechanisms that lead to inhibition of spermatogenesis because of a mutated androgen receptor are poorly understood and will need more focus in the future...
  21. ncbi request reprint Epidemiology and initial management of ambiguous genitalia at birth in Germany
    Ute Thyen
    Department of Pediatrics, University Medical Centre Schleswig Holstein, Campus Lubeck, Lubeck, Germany
    Horm Res 66:195-203. 2006
    ..In this epidemiological study, we sought to capture the incidence of ambiguous genitalia in neonates and to describe initial management strategies...
  22. doi request reprint Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1
    Maik Welzel
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Schleswig Holstein, Christian Albrechts University, Kiel, Germany
    Eur J Endocrinol 168:707-15. 2013
    ..In the latter, affected children suffer from neonatal onset of multi-organ salt loss and often exhibit cystic fibrosis-like pulmonary symptoms...
  23. ncbi request reprint Molecular androgen memory in sex development
    Paul Martin Holterhus
    Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Christian Albrechts University of Kiel and University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany
    Pediatr Endocrinol Rev 9:515-8. 2011
    ..In essence, there is evidence for a molecular androgen memory at both the transcriptome and the epigenome level...
  24. ncbi request reprint The clinical and molecular spectrum of androgen insensitivity syndromes
    O Hiort
    Department of Pediatrics, Medical University of Lubeck, Germany
    Am J Med Genet 63:218-22. 1996
    ..We conclude that mutations in the androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist...
  25. ncbi request reprint Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group
    G H Sinnecker
    Department of Paediatrics, Medical University of Lubeck, Germany
    Eur J Pediatr 156:7-14. 1997
    ..6%-62.1%). Differences between controls and each AIS group were statistically significant (P < 0.05 - < 0.0001). A close correlation was found between the degree of undermasculinization (AIS phenotype) and the SHBG response...
  26. ncbi request reprint Inherited and de novo androgen receptor gene mutations: investigation of single-case families
    O Hiort
    Department of Pediatrics, Medical University of Lubeck, Wolfsburg, Germany
    J Pediatr 132:939-43. 1998
    ..The objective of this study was to assess somatic and inherited androgen receptor gene mutations in families with only one affected individual...
  27. ncbi request reprint Puberty in disorders of somatosexual differentiation
    Olaf Hiort
    Department of Pediatrics, University Hospital of Lübeck, Germany
    J Pediatr Endocrinol Metab 16:297-306. 2003
    ..In this review we focus not only on the molecular impact of sex steroid action, but also view current opinions and studies on the gender development of the intersex patient during puberty...
  28. ncbi request reprint Clinical and molecular spectrum of somatic mosaicism in androgen insensitivity syndrome
    P M Holterhus
    Department of Pediatrics, Medical University, Lubeck, Germany
    Pediatr Res 46:684-90. 1999
    ..The possibility of functionally relevant expression of the wild-type AR needs to be considered in all mosaic individuals, and treatment should be adjusted accordingly...
  29. doi request reprint Functional and structural consequences of a novel point mutation in the CYP21A2 gene causing congenital adrenal hyperplasia: potential relevance of helix C for P450 oxidoreductase-21-hydroxylase interaction
    Felix G Riepe
    Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Schleswig Holstein, Schwanenweg 20, Kiel, Germany
    J Clin Endocrinol Metab 93:2891-5. 2008
    ..Congenital adrenal hyperplasia is caused by insufficient adrenal steroid biosynthesis due to impaired steroidogenic enzymes. The majority of patients suffer from deficiency of 21-hydroxylase (CYP21) coded by the CYP21A2 gene...
  30. ncbi request reprint Classification of distinct baseline insulin infusion patterns in children and adolescents with type 1 diabetes on continuous subcutaneous insulin infusion therapy
    Paul Martin Holterhus
    Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Christian Albrechts Universitat zu Kiel, Universitätsklinikum Schleswig Holstein Campus Kiel, Kiel, Germany
    Diabetes Care 30:568-73. 2007
    ..We aimed at classification of basal insulin infusion rate regimens and comparing patients' underlying clinical characteristics...
  31. ncbi request reprint Exclusion of serum- and glucocorticoid-induced kinase 1 (SGK1) as a candidate gene for genetically heterogeneous renal pseudohypoaldosteronism type I in eight families
    Felix G Riepe
    Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany
    Am J Nephrol 27:164-9. 2007
    ..Therefore variations in the SGK1 gene may aggravate renal salt loss or cause PHA1...
  32. ncbi request reprint A unique exonic splicing mutation in the human androgen receptor gene indicates a physiologic relevance of regular androgen receptor transcript variants
    O J Hellwinkel
    Department of Pediatrics, , , Germany
    J Clin Endocrinol Metab 86:2569-75. 2001
    ....
  33. doi request reprint A novel ultrapressure liquid chromatography tandem mass spectrometry method for the simultaneous determination of androstenedione, testosterone, and dihydrotestosterone in pediatric blood samples: age- and sex-specific reference data
    A E Kulle
    Department of Pediatrics, Christian Albrechts University of Kiel, 24105 Kiel, Germany
    J Clin Endocrinol Metab 95:2399-409. 2010
    ..Mass spectrometry-based methods are available for individual steroids but need complex sample preparation and report only fragmentary reference data for the pediatric population...
  34. doi request reprint No correlation between androgen receptor CAG and GGN repeat length and the degree of genital virilization in females with 21-hydroxylase deficiency
    M Welzel
    Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Christian Albrechts University, Schwanenweg 20, D 24105 Kiel, Germany
    J Clin Endocrinol Metab 95:2443-50. 2010
    ..However, genital virilization in affected females correlates only weakly with CYP21A2 mutation groups, suggesting the influence of genetic modifiers...
  35. ncbi request reprint The A645D mutation in the hinge region of the human androgen receptor (AR) gene modulates AR activity, depending on the context of the polymorphic glutamine and glycine repeats
    Ralf Werner
    Department of Pediatric and Adolescent Medicine, University of Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany
    J Clin Endocrinol Metab 91:3515-20. 2006
    ..In addition, they also harbor a rare A645D substitution...
  36. ncbi request reprint Deciding on gender in children with intersex conditions: considerations and controversies
    Ute Thyen
    Department of Child and Adolescent Medicine, University Hospital Schleswig Holstein, Campus Lubeck, University of Lubeck, Lubeck, Germany
    Treat Endocrinol 4:1-8. 2005
    ....
  37. ncbi request reprint Androgen receptor gene mutations in androgen insensitivity syndrome cause distinct patterns of reduced activation of androgen-responsive promoter constructs
    Ralf Werner
    Department of Pediatric and Adolescent Medicine, University of Lubeck, Germany
    J Steroid Biochem Mol Biol 101:1-10. 2006
    ..Assessment of transactivation patterns in vitro may be an interesting concept to extend functional description of AR-gene mutations in AIS...
  38. ncbi request reprint Cell-line and tissue-specific signatures of androgen receptor-coregulator transcription
    Jan Hendrik Bebermeier
    Department of Pediatric and Adolescent Medicine, University Hospital Schleswig Holstein, Campus Lubeck, Lubeck, Germany
    J Mol Med (Berl) 84:919-31. 2006
    ..Therefore, differential expression patterns of AR coregulators could modify tissue-specificity and diversity of androgen actions in development, physiology, and disease...
  39. ncbi request reprint Gender role behavior in children with XY karyotype and disorders of sex development
    Martina Jürgensen
    Department of Child and Adolescent Medicine, University Hospital Schleswig Holstein, Campus Lubeck, Ratzeburger Allee 160, D 23538 Lubeck, Germany
    Horm Behav 51:443-53. 2007
    ..We conclude that androgen exposure plays a decisive role in the development of gender-typical behavior in children with XY karyotype and DSD conditions...