Wednesday, July 31, 2013

ESTROGENIC RELATED EVENTS ARE STILL POORLY UNDERSTOOD!

In the life of of women, there is no event that has such profound implications than the onset of the reproductive phase! or the reign of Estrogen!   Clearly, there are 3 phases to women's genetic life in our humble view:
Phase I life before Reproductive life
Phase II life during Reproductive life
Phase III life after Reproductive life

And in each phase, only Estrogen and related proteins make a difference by their absence or presence!
During phase I, the gene life is mostly influenced by the presence of the active X gene and "maturing" of all class of HLA genes as exposure to antigens of all kind occurs!

The rise of Estrogen in the second phase, deeply changes class I HLA expression to prepare the female body to receive a "foreign" body of an eventual infant!  Many genes will be suppressed.  And one of the ways they are suppressed is through hyper-Methylation.  To this day, we do not have a sufficient description of the patterns of methylation that occur at this particular time!  Understanding these epigenetic events has turned out to be critical  Just one example that points to the importance of these events, are the high rates of complications with Lupus (and other autoimmune diseases) in women during this second phase.  And remember, most congenital genetic based cancers express themselves during this period of time, that is why we suspect them to be genetic based (first clue in oncology practice)!  i.e.Triple negative Breast cancer in a 30 Year old! Gives you the aha moment!

The retirement of Estrogen in the IIIrd phase induces so much cardiovascular havoc that books have been written about the devastations of menopause!

Describing patterns of epigenetic events in women in each phase is so critical and complicated we simply run away from it!  But now, taking back courage, we are starting to look at it!

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