Histone deacetylase inhibitor may prevent pre-term labour in women
Pre-term labour in women could be prevented using a histone deacetylase inhibitor to alter progesterone receptors, say researchers from the University of Texas Southwestern Medical Centre, Dallas.
The researchers have found a way to delay pregnant mice from going into
labour for 24–48 hours. This is significant since the average length
of gestation in the mouse is only 19 days, and the authors say that the
biochemical steps associated with labour are likely to be the same in
mice and humans.
Elevated progesterone levels prevent the uterus from contracting throughout
a normal pregnancy. The researchers postulate that labour is caused by
a number of factors that prevent progesterone from acting. They examined
tissues taken from the myometria of women at the end of pregnancy and
in labour, and found a marked decline in proteins containing histone
acetylase activity at this time. Such activity alters the structure around
progesterone-responsive genes, antagonising progesterone receptor function.
The researchers found that administration of trichostatin A, a specific
and potent histone deacetylase inhibitor, to pregnant mice in late gestation
increased histone acetylation in the uterus, allowing the progesterone
receptors to continue functioning (Proceedings of the National Academy of Sciences 2003;100:9518). |
