It also is clear from the present data that microvascular growth cannot account for the early and substantial increase in uterine blood flow that occurs within 30-60 min after estrogen treatment in ovariectomized mammals and that is probably due exclusively to vasodilation of the uterine vascular bed. Nevertheless, the sustained increase in uterine blood flow that occurs throughout pregnancy is probably due primarily to growth of the entire uterine vascular bed, including the uterine arteries. In addition, a portion of the angiogenic response of the uterus, including the up-regulation of endometrial angiogenic factor expression, may be caused by the early increase in uterine blood flow, since sheer-stress resulting from increased flow has been shown to induce angiogenesis in a variety of tissues. buy flovent inhaler
In conclusion, we have shown that the uterine growth in OVX, E2-treated sheep is due to hyperplasia and hypertrophy, with only a relatively small change in the tissue dry weight:fresh weight ratio. The most dramatic uterine growth occurred between 8 and 48 h after E2 treatment and was associated with increased cell proliferation in all of the uterine tissue compartments. In addition, the uterine growth response was associated with an even more dramatic increase in the volume of endometrial microvasculature. These studies will provide a foundation for further elucidation of the mechanisms responsible for uterine growth and microvascular development in response to steroids. For example, in a companion paper, we have investigated endometrial expression of two major angiogenic factors, namely basic fibroblast growth factor and vascular endothelial growth factor, and related the expression of these factors to the microvascular response observed in the present study.