Comparison of the Effects of Gossypol, Estradiol-17β and Testosterone Compensation on Male Rat Reproductive Organs

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Abstract
The effects of gossypol acetic acid (GAA) were compared with those induced by estradiol-17.beta. (E2), testosterone, and a combination of these steroids. GAA was administered s.c. to adult rats at doses of 25-30 mg .cntdot. kg .cntdot. body weight .cntdot. day for 30 days, while steroids in polydimethylsiloxane tubing of various lengths were implanted s.c. for 30 days or longer. GAA and E2 at the doses used had similar effects: they caused a graded atrophy of sex organs, discriminative degeneration of spermatogenic cells, impairment of Sertoli cells, decrease in serum testosterone, reduction in androgen receptor binding and retardation in body growth. Supplementing GAA and E2 treatments with 14-cm testosterone implants had a counteracting effect on organ weight losses: seminal vesicles recovered above, ventral prostate within and epididymides below control values, whereas the testes did not respond. The organs most refractory to supplementation therapy were those in which GAA and E2 were most effective in depressing androgen receptor binding. Aside from having similar antiandrogenic effects as E2 and other steroids, GAA induced a specific flagellar syndrome which testosterone therapy could not prevent, indicating that this action is hormonally independent.