Effect of aromatase inhibitors on the histology of the cycling rat ovary

Two aromatase inhibitors, 4-hydroxyandrostenedione (4-OHA) and testololactone (Teslac), were tested to determine their effects on folliculogenesis, particularly ovarian histologic alterations, in the cycling rat. Adult, female Sprague-Dawley rats were treated with continuous infusion of both inhibitors at concentrations of 10⁻⁸, 10⁻⁴, and 10⁻² M for 30 days. The effect of the inhibitors on cultured granulosa cells harvested on procstrus was determined in vitro. The in vivo administration of each inhibitor induced significant reduction in ovarian-vein estradiol levels. Estradiol synthesis in cultured granulosa cells was inhibited by both aromatase inhibitors in a dosc-dcpcndcnl fashion. These observations indicate that 4-OHA and Teslac significantly inhibit basal estradiol synthesis in vivo and in vitro. This effect on estrogen synthesis was not reflected in alteration of the ovarian histology in the cycling rat.