Effects of Estradiol Benzoate on Thyroid-Pituitary Function in Female Rats*

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Abstract
Effects of ovariectomy (ovx) and ovx with estradiol benzoate (EB) therapy on total and free T3 [triiodothyronine] (F[free]T3), T4 [thyroxine], and [125I]T3 disappearance rate; basal and post-TRH [thyroliberin], TSH [thyrotropin], T3, and T4 concentrations were studied in female rats. Two weeks after ovx, no significant change in hormone concentrations was observed. Two micrograms of EB daily for 1 wk significantly increased basal serum TSH by 40% and serum total T3 by 25-30%, but decreased serum T4 by 50%. The percentage of FT3 and free T4 (FT4) did not differ in the sham-operated intact, ovx, and ovx-EB-treated animals, resulting in an increase in total absolute FT3 and a decrease in FT4 by EB. [125I]T3 plasma disappearance rate was not altered by either ovx or EB. Ten minutes after TRH, serum TSH increased 6- to 7-fold in both the intact and ovx rats, but increased 10- to 13-fold in the EB-treated animals. Two hours after TRH, a significant increase in serum T3 concentration was observed in all groups of animals, but the absolute incremental T3 response after EB was significantly greater than in the other 2 groups. No change in serum T4 was observed 2 h after TRH in all groups. When ovx female rats were treated with graded doses of EB, ranging from 0-10 .mu.g EB/day for 7 days, serum T3 concentrations increased in a dose-dependent manner while T4 decreased reciprocally, with a maximum effect at the 2 .mu.g/day EB dose. When female rats were ovariectomized and thyroidectomized for 3 wk and then treated with 3 .mu.g/100 g BW [body wt] with or without 2 or 10 .mu.g EB for 12 days, serum T3 concentrations in the EB-treated animals were 2-fold those of the controls and T4 concentrations decreased in the EB-treated rats. EB increased both TSH and T3 serum concentrations for both basal and post-TRH values but decreased basal total and FT4; the increase in serum total and free T3 was not due to changes in either peripheral T3 clearance or plasma binding; and the increased basal and post-TRH TSH levels from EB may be due not only to its direct central effect on pituitary thyrotropes but also to its peripheral action to induce changes in total and free T4 and T3 concentrations by an enhanced extrathyroidal conversion of T4 to T3.