Cargando…

Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes

BACKGROUND: Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of pe...

Descripción completa

Detalles Bibliográficos
Autores principales: Holterhus, Paul-Martin, Bebermeier, Jan-Hendrik, Werner, Ralf, Demeter, Janos, Richter-Unruh, Annette, Cario, Gunnar, Appari, Mahesh, Siebert, Reiner, Riepe, Felix, Brooks, James D, Hiort, Olaf
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713997/
https://www.ncbi.nlm.nih.gov/pubmed/19570224
http://dx.doi.org/10.1186/1471-2164-10-292
_version_ 1782169623049797632
author Holterhus, Paul-Martin
Bebermeier, Jan-Hendrik
Werner, Ralf
Demeter, Janos
Richter-Unruh, Annette
Cario, Gunnar
Appari, Mahesh
Siebert, Reiner
Riepe, Felix
Brooks, James D
Hiort, Olaf
author_facet Holterhus, Paul-Martin
Bebermeier, Jan-Hendrik
Werner, Ralf
Demeter, Janos
Richter-Unruh, Annette
Cario, Gunnar
Appari, Mahesh
Siebert, Reiner
Riepe, Felix
Brooks, James D
Hiort, Olaf
author_sort Holterhus, Paul-Martin
collection PubMed
description BACKGROUND: Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells (PBMC) in patients with rare defined "disorders of sex development" (DSD, e.g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46, XY-males and 46, XX-females. RESULTS: A discrete set of transcripts was directly correlated with XY or XX genotypes in all individuals independent of male or female phenotype of the external genitalia. However, a significantly larger gene set in the PBMC only reflected the degree of external genital masculinization independent of the sex chromosomes and independent of concurrent post-natal sex steroid hormone levels. Consequently, the architecture of the transcriptional PBMC-"sexes" was either male, female or even "intersex" with a discordant alignment of the DSD individuals' genetic and hormonal sex signatures. CONCLUSION: A significant fraction of gene expression differences between males and females in the human appears to have its roots in early embryogenesis and is not only caused by sex chromosomes but also by long-term sex-specific hormonal programming due to presence or absence of androgen during the time of external genital masculinization. Genetic sex and the androgen milieu during embryonic development might therefore independently modulate functional traits, phenotype and diseases associated with male or female gender as well as with DSD conditions.
format Text
id pubmed-2713997
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-27139972009-07-23 Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes Holterhus, Paul-Martin Bebermeier, Jan-Hendrik Werner, Ralf Demeter, Janos Richter-Unruh, Annette Cario, Gunnar Appari, Mahesh Siebert, Reiner Riepe, Felix Brooks, James D Hiort, Olaf BMC Genomics Research Article BACKGROUND: Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells (PBMC) in patients with rare defined "disorders of sex development" (DSD, e.g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46, XY-males and 46, XX-females. RESULTS: A discrete set of transcripts was directly correlated with XY or XX genotypes in all individuals independent of male or female phenotype of the external genitalia. However, a significantly larger gene set in the PBMC only reflected the degree of external genital masculinization independent of the sex chromosomes and independent of concurrent post-natal sex steroid hormone levels. Consequently, the architecture of the transcriptional PBMC-"sexes" was either male, female or even "intersex" with a discordant alignment of the DSD individuals' genetic and hormonal sex signatures. CONCLUSION: A significant fraction of gene expression differences between males and females in the human appears to have its roots in early embryogenesis and is not only caused by sex chromosomes but also by long-term sex-specific hormonal programming due to presence or absence of androgen during the time of external genital masculinization. Genetic sex and the androgen milieu during embryonic development might therefore independently modulate functional traits, phenotype and diseases associated with male or female gender as well as with DSD conditions. BioMed Central 2009-07-01 /pmc/articles/PMC2713997/ /pubmed/19570224 http://dx.doi.org/10.1186/1471-2164-10-292 Text en Copyright © 2009 Holterhus et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Holterhus, Paul-Martin
Bebermeier, Jan-Hendrik
Werner, Ralf
Demeter, Janos
Richter-Unruh, Annette
Cario, Gunnar
Appari, Mahesh
Siebert, Reiner
Riepe, Felix
Brooks, James D
Hiort, Olaf
Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
title Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
title_full Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
title_fullStr Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
title_full_unstemmed Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
title_short Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
title_sort disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713997/
https://www.ncbi.nlm.nih.gov/pubmed/19570224
http://dx.doi.org/10.1186/1471-2164-10-292
work_keys_str_mv AT holterhuspaulmartin disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT bebermeierjanhendrik disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT wernerralf disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT demeterjanos disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT richterunruhannette disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT cariogunnar disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT apparimahesh disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT siebertreiner disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT riepefelix disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT brooksjamesd disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes
AT hiortolaf disordersofsexdevelopmentexposetranscriptionalautonomyofgeneticsexandandrogenprogrammedhormonalsexinhumanbloodleukocytes