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Uterine Bleeding
Uterine bleeding is part of a complex process that includes the
activation of homeostatic mechanisms coupled to regeneration of the
uterine lining. The cell biology of normal menstruation is not
completely understood. Recent evidence suggests that hormone withdrawal
leads to down regulation of uterine cell genes that control growth and
differentiation, programmed cell death, and the coordinated release of
matrix metalloproteinases and other proteins that degrade and remodel
the extracellular matrix and promote stem cell proliferation leading to
regeneration of the uterine lining. The endometrium also produces
proteins that govern homeostasis in a hormonally controlled fashion.
These processes may become deregulated when ovarian hormone production
is suboptimal during puberty or the perimenopausal period, when
anovulatory cycles are associated with irregular and/or excessive
bleeding. Furthermore, the mechanisms of the abnormal bleeding that
leads women to discontinue the use of contraceptives such as IUDs and
"progestin-only" methods are known to be different from those
associated with normal menses.
Although primary cultures of uterine cells and malignant endometrial
cell lines have been investigated for a number of years, systems that
replicate the complex interaction between epithelial, stromal, and
vascular cells of the uterus have yet to be devised. This has thwarted
the cellular and molecular exploration of the process of normal
menstruation and dysfunctional uterine bleeding. This difficulty is
further complicated by the lack of appropriate animal models for
abnormal bleeding.
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