Comparison of early morphological and molecular changes induced by 17-alpha-methyltestosterone and estradiol benzoate in the rat ovary.

Repeated exposure to 17-α-methyltestosterone (17MT) and estradiol benzoate (EB) for 28 or 90 days in rats induce similar ovarian atrophy. The objective of the present work was to identify and compare the early effects induced by 17MT and EB on the ovary using molecular and histopathological tools. Female rats were evaluated after 1, 3 or 7 days following an oral exposure by gavage at a daily dose of 600 mg/kg/day for 17MT and 5 mg/kg/day for EB. All animals were found to be acyclic after 3 or 7 days of treatment with 17MT and EB. Histopathological changes were present in the ovary, uterus, vagina and mammary gland after both treatments. Ovarian atrophy known as the long term effect of 17MT and EB was not yet detected after 7 days of treatment. But non regressive corpora lutea and cystic follicles were identically observed in the ovary of 17MT and EB treated females. Both compounds induced a decrease of LH transcripts together with an increase of plasma progesterone and prolactin levels. Differences in the profile of regulation of the aromatase were noted after 1 and 3 days of treatment in 17MT treated animals (upregulated) when compared to EB treated animals (downregulated). In summary, we have shown that despite the different nature of hormonal activity, EB and 17MT induce very early endocrine perturbation which presents several similarities. Our work indicated that the detection of early key hormonal markers in short term studies can help to predict the adverse long term effects on target tissues.