Sexually dimorphic gene expression in somatic tissues. Authors: J. Isensee and P.Ruiz Noppinger

1. Sexually dimorphic gene expression in somatic tissues. Authors: J. Isensee and P.Ruiz Noppinger Center for Cardiovascular Research, Center for Gender in Medicine Max-Planck Institute for Molecular Genetics, Berlin, Germany Not gene after gene but 25.000 genes simultaneous: DNA microarrays

2. 1. DIFFERENCES DUE TO THE ANALYTICAL PLATFORM: The most prominent overlap of 87 genes was found between the studies of Yang et al. and Clodfelter et al. both conducted using the Agilent platform. This finding clearly indicates that the platform has a major impact on the detectable sexual dimorphisms. Significantly fewer genes were detected by the Affymetrix platform with only one gene (Uty) being exclusively detected by this platform. 2. Gene results are translated to processes like “steroid synthesis” or “fatty acid metabolism” by gene ontology annotation (David) Could the results also be analysed by pathway-analysis programs like GeneMapp to find molecular pathways?

3. 3. Since most of the sexually dimorphic genes displayed <1.2-fold changes • between males and females • 81.3% for liver, • 71.4% for adipose tissue, • 82.5% for muscle, • 94.4% for brain • sex differences seem wide spread, but of minor extent. • Should be given more attention if changes are significant!

4. 4. Abstract. This review focuses on basic regulatory mechanisms of sex-specific gene expression and discusses recent gene expression profiling studies to outline basic differences between sexes on transcriptome level in somatic tissues. In rodents as well as in humans GH is released from alpha cells in the anterior pituitary in males in a cyclical manner with high amplitudes. In females, smaller amplitudes and higher pulse frequencies are leading to a more constant plasma level. Genomic and nongenomic actions of sex steroid hormones might converge on the regulation of target genes via signal transduction pathways modulating the activity of several transcription factors. Hormone binding also induces the recruitment of a broad array of Co-regulatory proteins. Cell-specific expression of co-regulatory proteins and their modulation by posttranslational modifications allow tissue-specific and temporal steroid hormone receptor-mediated transcription.

5. 5. In rodents as well as in humans GH is released from alpha cells in the anterior pituitary in males in a cyclical manner with high amplitudes. In females, smaller amplitudes and higher pulse frequencies are leading to a more constant plasma level. Consequences but not causes are mentioned • 6. Despite the sex chromosomal genotype no phenotypical differences • between sexes are present during the early embryonic development • of mammals. The first event of sexually dimorphic development is the • differentiation of the bipotential gonad into testis or ovary. • Barker theory of fetal programming: • gender differences risk for later life diseases are • laid down in the fetal phase (behavior)

6. 7. Data of current studies clearly indicate that the sex-biased expression of genes is highly tissue-specific Are there tissue-specific sex-organizers? or Are there sex-specific tissue-organizers? • 8.What are the consequences/use of this type of knowledge for society? • Can sexual dimorphism of gene expression in brain be examined in humans? • What would be the meaning of knowing that male and female brain-genes • are differently expressed? • Could we then better understand sex-dependent behavior?

7. CONCLUSIONS: GENOMICS IS A NEW TECHNOLOGY • Robustness • Reliability/validation • Handling of large datasets • Animal studies • Expensive • Descriptive • Large scale quantification of molecular sex differences • Continue and expand studies ??? • -Human • -Prenatal • -Mechanistic • -> ethical issues • -> what will this lead to