Ornithine decarboxylase activity as a marker of androgen and antiandrogen action in the rat epididymis

Abstract

After castration, there was a marked decrease in serum androgen concentration at 6 h, and a dramatic inhibition of ornithine decarboxylase (ODC) at 12 h. Administration of testosterone propionate to castrated rats at a dose of 0.05 mg/animal restored ODC activity to the normal value. However, no change was observed when intact rats were treated with testosterone even at a 40-fold higher dose, indicating that endogenous androgens present in intact rats are far in excess for maintenance of maximal levels of activity. Administration of the antiandrogen flutamide to intact rats caused a moderate decrease in epididymal weight, whereas this effect was more pronounced in castrated, androgen-treated rats. In the latter, the effect of flutamide was significant at the lowest dose used (0.5 mg/day). ODC activity was significantly decreased by flutamide treatment of intact rats, but even at the highest dose used (10 mg/day) only a 39% inhibition was observed. In flutamide-treated rats, LH concentrations were markedly increased, as were serum and epididymal androgens. In androgen-treated castrated rats, flutamide caused epididymal ODC to fall to undetectable values. These results show that: (1) androgens are essential for the maintenance of ODC activity in the epididymis; (2) epididymal ODC activity is maximally stimulated by endogenous androgens, at least in the pubertal rat; (3) the apparent potency of flutamide is substantially lowered by an increase in epididymal androgens. We suggest that ODC is a sensitive marker of the action of androgens and antiandrogens in the epididymis.

Ornithine Decarboxylase Activity and Polyamine Levels in the Epididymis of Prepubertal Rat After Antiandrogen Administration

“…Moreover, the reduction in epididymal weight after flutamide treatment observed in the present study was more pronounced than that seen in pubertal rats [9]. A lower dose of flutamide (1 mg) was enough to detect a significant decrease in epididymal weight.…”

“…The present results show that flutamide administration to prepubertal rats cause a pronounced decay in epididymal ODC activity. In fact, a lesser decrease has previously been detected in pubertal rats [ 9 ] . On the other hand, casodex administration provoked an evident diminution in epididymal ODC activity, although the levels reached were not so low as with flutamide.…”

“…Epididymal androgens were extracted and measured by the method validated in this laboratory [24] with minor modifications for this tissue [9]. Dihydrotestosterone (DHT) and 5a-androstane-3a, 17p-diol (Diol) were measured by radioimmunoassay using highly specific antibodies (DHT-1 -CMO-BSA and Diol-15-CMO-BSA).…”

“…On the other hand, nonsteroidal antiandrogens have become a reliable tool to study the role of androgens on sex accessory organs. In pubertal intact rats, administration of flutamide caused a significant but moderate decrease in epididymal weight and ODC activity [9]. Even more important, flutamide did not affect either the content or the concentration of polyamines in the epididymis of intact adult rats; when flutamide was administered to castrated androgen treated rats, it was detected a significant decline in putrescine content [lo].…”

“…ODC activity is a sensitive marker of flutamide action in the epididymis of pubertal rats [9]. Until now, no studies have evaluated the antiandrogenic effect on epididymal ODC activity during the prepubertal period.…”