Modulierung der Signaltransduktion durch eine neues Exon im LH-Rezeptorgen
Final Report Abstract
In the last three years we could get a deeper insight into the compley regulation of the CGLHR at the epigenetic, transcriptional levels which helped to understand distinct pathophysiologies caused by a defective receptor. We could demonstrate the impact of the novel, primate specific exon 6A for receptor functioning. Disorder of sexual development can be caused by mutations of exon 6A. We could show that the receptor regulation is mediated by DNA methylation and by a specific miRNA which regulate receptor expression at the transcriptional level. Unfortunately and despite many efforts we did not convincingly address the question of the truncated form of the exon 6 CGLHR to act as a hormone scavenger. The collaboration with our Finnish colleagues on the generation of a humanized CGLHR mouse model is continuing and hopefully will give new insights in receptor diversity and specificity. We suggested a new nomenclature for the classification of the different LH receptor form in different species, dependent on the presence of exons (exon 10 and exon 6A) and/or LH/CG.
Publications
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4th Congress of the International Network for Young Researchers in Male Fertility (2011): Mutations in Exon 6a of the Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene Cause Leydig Cell Hypoplasia
Britta Troppmann, Nina Kossack, Annette Richter-Unruh, Gunnar Kleinau, Jörg Gromoll
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Bregenzer Summer School (2012) Impact of mutations in exon 6A on the structure of the Luteinizing Hormone/Chorionic Gonadotropin Receptor
Britta Troppmann, Nina Kossack, Annette Richter-Unruh, Gunnar Kleinau, Jörg Gromoll
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(2013) Aberrant transcription of the LHCGR gene caused by a mutation in exon 6A leads to Leydig cell hypoplasia type II. Mol Cell Endocrinol. 366, 59-67
Kossack N., Troppmann B., Richter-Unruh A., Kleinau G., Gromoll J.
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(2013) Structural and functional plasticity of the luteinizing hormone/choriogonadotropin receptor. Human Reprod. Update. 5:583-602
Troppmann B., Kleinau G., Krause G., Gromoll J.
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56. Symposium Deutsche Gesellschaft für Endokrinologie (2013): Impact of DNA methylation on the expression regulation of the LHCGR
Selig J.I., Troppmann B., Gromoll J.
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56. Symposium Deutsche Gesellschaft für Endokrinologie (2013): Mutations in Exon 6a of the Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene Cause Leydig Cell Hypoplasia
Britta Troppmann, Nina Kossack, Annette Richter-Unruh, Gunnar Kleinau, Jörg Gromoll
