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 (ODC) activity was measured in epididymides of 45-day-old rats. Higher ODC activity was detected in the corpus and cauda than in the caput epididymidis. Bilateral castration for 7 days caused epididymal ODC to fall to undetectable values, whereas testosterone restored activity to normal values. The effect of the androgen was significantly inhibited by cyproterone acetate. The caput was more sensitive to the action of testosterone than were the corpus and caudal segments. Unilateral castration for 4 or 8 days did not affect ODC on the control or castrated side, but the activity fell in epididymides of both sides after removal of the remaining testis. These results show that epididymal ODC activity is androgen-dependent.

Flutamide is a nonsteroidal antiandrogen that blocks androgen receptors, with a consequent increase in serum immunoreactive LH (I-LH) in the presence of high testosterone concentrations. Several studies suggested that the gonadal steroids also play an important role in the regulation of LH bioactivity (B-LH). Therefore, it seems difficult to understand how the blockade of pituitary androgen receptors leads to the increase in testosterone levels. The present study was designed to elucidate the effect of flutamide on serum I-LH, B-LH and testosterone, as well as on in vitro stimulation of pituitaries by gonadotropin-releasing hormone (GnRH), in intact and androgen-treated castrated rats. In intact animals, a dose of flutamide as low as 0.5 mg/day provoked a 7- to 8-fold increase in serum I-LH levels over the vehicle-injected controls, whereas B-LH and testosterone were unaffected. However, higher doses significantly increased serum B-LH to values similar to those obtained in vehicle-injected castrated animals, resulting in high testosterone levels. Flutamide treatment provoked a decrease in I-LH and B-LH pituitary content; this effect was significantly higher under in vitro GnRH stimulation. The releasable I-LH under GnRH stimulation was not affected by flutamide treatment; however, a marked decrease was observed in B-LH. The results presented here show that (1) the interference of androgen action by flutamide is as efficient as castration to affect I-LH and B-LH; (2) androgens may act directly at the pituitary level; (3) androgens modulate the action of GnRH in the pituitary gland, and (4) the effect of androgens on the pituitary can be observed at two distinct levels, depending on the androgen concentration, that is on LH synthesis and release, and on LH bioactivity. In addition, our results confirm that high doses of flutamide are not enough to abolish the biological action of androgens, due to the increase in LH bioactivity resulting in high androgen concentrations.

High K+ medium and glutamate elicited a significant [3H]-GABA release in the golden hamster retina. High K+ -induced GABA release was largely calcium-dependent, while the effect of glutamate was Ca2+ -independent. After replacing Na+ by Li+, glutamate-evoked [3H]-GABA release was abolished, while high K+ -evoked release remained unchanged. The effect of glutamate was completely blocked by DNQX but not by APV. Furthermore, kainate induced [3H]-GABA release, whereas NMDA was ineffective. Assessment of endogenous GABA efflux further confirmed results obtained for [3H]-GABA. GABA-like immunoreactivity was observed in amacrine cells, in neurons localized in ganglion cell layer, as well as in fibers and terminals at the inner plexiform layer. In addition a few horizontal cells showed GABA-like immunolabeling. The present results suggest the existence of at least two pools of GABA in the hamster retina, compatible with both vesicular and carrier-mediated mechanisms of transmitter release, being the amacrine cells the main gabaergic source in this tissue.

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