Relationship Between Early Vascular Responses and Growth in the Rat Uterus: Stimulation of Cell Division by Estradiol and Vasodilating Amines

Abstract

The influence of estradiol and of vasodilating amines on hyperemia, edema production and growth in uteri of ovariectomized rats was determined. Estradiol (0.04 μg), histamine (0.3 mg), 5-hydroxytryptamine (serotonin, 0.2 mg), 3-(β-aminoethyl) pyrazole (Histalog, 0.2-0.3 mg) or saline was injected into the uterine lumina of rats maintained under controlled lighting and temperature. Solutions were pre-adjusted to pH 7.0. The experimental substances caused significant increases in uterine water content in 4 hr from a level of 79.5 % (saline) to 82–83% (serotonin, histamine) and 84% (estradiol). Histalog, a histamine analogue, produced negligible hydration. Cross sections of uteri from colchicine-treated rats sacrificed 24 hr after injection of control or experimental solutions were examined for evidence of growth stimulation. All luminal epithelial cells in metaphase as well as the total number of epithelial cells in each of 8–16 sections/rat were counted. Calculations of the number of cells in metaphase /1,000 cells revealed increases in cell division over saline-injected uteri of 112% (estradiol) and 74% (histamine or serotonin), whereas Histalog produced no significant change. Cortisol (3.5 mg/100 g body wt), given iv at the same time as estradiol or histamine, significantly depressed both the edema at 4 hr and the cell division at 24 hr normally stimulated by estradiol or histamine alone. These data support the views that hyperemia and edema, stimulated by estrogen in uterus, are related to growth as causative factors and that endogenous histamine normally mediates the vascular responses to estrogen.