Sexually dimorphic gene expression in somatic tissues.

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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
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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?
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3. Since most of the sexually dimorphic genes
displayed lt1.2-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!
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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.
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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)
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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?

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• 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
• -gt ethical issues
• -gt what will this lead to