Cohorts of mice were sacrificed 48 hours following each estradiol injection, and at three other equidistant time points. Serum and ovarian tissue estradiol concentration was correlated to immunohistochemical and morphometric parameters used to identify evidence of OSE hyperplasia and hypertrophy. Using immunohistochemistry, E-cadherin expression was investigated in OSE 48 hours following both estradiol injections, while ER伪 and ER尾1 expression was examined in OSE following repeat estradiol exposure only.
First exposure to exogenous estradiol resulted in OSE hypertrophy and hyperplasia, and high levels of E-cadherin expression. In contrast, repeat estradiol exposure resulted in no OSE hyperplasia or hypertrophy, low levels of E-cadherin expression, high ER伪 and reduced ER尾1 protein expression in OSE, and low stromal ER伪 expression. Blood and ovarian tissue estradiol levels following repeat estradiol injection were half those recorded after a first dose equivalent injection, but remained significantly elevated above controls.
Repeat estradiol exposure leads to accumulation of estradiol in ovarian tissue, differentially regulating protein expression patterns for E-cadherin in OSE and ER in OSE and stroma.