The Antiandrogenic Effects of Δ1-Testolactone (Teslac) in Vivo in Rats and in Vitro in Human Cultured Fibroblasts, Rat Mammary Carcinoma Cells, and Rat Prostate Cytosol*

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Abstract
The antiandrogenic properties of Δ1-testolactone (17β-oxa-D-homo-l,4-androstane-3,17-dione; Teslac) were investigated in vivo and in vitro. Teslac (75 mg/day for 7 days) inhibited the rise in ventral prostate weight induced by testosterone (T) (P < 0.001), dihydrotestosterone (DHT) (P < 0.05), and a combination of T plus 17β-estradiol (E2) (P < 0.01) in immature castrate rats. Similar effects were seen on the seminal vesicles after T and T plus E2 (P < 0.001). Teslac also decreased prostate and seminal vesicle weights in intact immature rats. The effects of Teslac were dose and time dependent. Teslac did not change the concentration of serum T or DHT. However, Teslac inhibited DHT binding to the androgen receptor (Ki = 2.5 ± 0.8 × 10-7 M) in cytosol of the rat prostate. Teslac also inhibited DHT binding to the androgen receptor in cultured human prepuce fibroblasts and cultured rat mammary tumor cells (Ki = 1.9 ± 0.3 × 10-5 M). The results indicate that Teslac, in addition to its antiaromatase activity, is an antiandrogen by virtue of its interaction with the androgen receptor.