Androgen-induced nuclear accumulation of the estrogen receptor

Abstract

The effect of androgens on the nuclear uptake of both tritiated estradiol ( 3H-E 2) and the estrogen receptor was studied in immature rat uteri. It was demonstrated that in vitro preincubation of immature rat uteri with various androgens (1 μM to 50μM) followed by incubation with 3H-E 2 (20nM) resulted in a greatly decreased specific nuclear uptake of 3H-E 2. Non-androgenic steroids had no effect. It was also confirmed that 5a-dihydrotestosterone (DHT) causes the accumulation of the estrogen receptor in the nuclei of uterine tissue. In vitro incubations of rat uteri with DHT (1μM and 50μM) were found to cause maximal nuclear estrogen receptor accumulation to the same degree as caused by estradiol, i.e. the nuclear uptake of approximately 100% of the estrogen receptor. Antiandrogens, which block the binding of androgens to the testosterone receptor in various tissues, did not inhibit the DHT -induced decrease in the 3H-E 2uptake by the uterine nuclei or the DHT — caused accumulation of the estrogen receptor in nuclei. These results seem to indicate that the uterine testosterone receptor has no role in the androgen — induced nuclear uptake of the estrogen receptor. However, the non-steroidal antiestrogens inhibited the DHT — induced nuclear accumulation of the estrogen receptor. This would seem to indicate that the estrogen — and androgen — induced nuclear accumulation of the estrogen receptor share a common mechanism.