AIMTo investigate the effect of diethylstilbestrol (DES), one of the most potent endocrine disruptors, on the metabolism of polyamines in hamster epididymis.

METHODSMale golden hamsters of 7-week-old were kept under a light and dark cycle of 14 h and 10 h for 1 week to stimulate maximally the gonadal function. DES was injected subcutaneously at doses of 0.01 mg . kg(-1) . day(-1), 0.1 mg . kg(-1) . day(-1) and 1 mg . kg(-1) . day(-1) for one week.

RESULTSDES treatment caused a significant decrease in the weight of epididymis. The activity of epididymal ornithine decarboxylase (ODC) increased 1 day after DES treatment, kept at a high level for 4 days and then decreased to nearly normal level at day 7. The activity of spermidine/spermine N1-acetyltransferase (SSAT) also increased transiently after DES treatment. The contents of putrescine, spermidine, spermine and N(1)-acetylspermidine were increased 1 day approximately 4 days after DES treatment and restored to normal at day 7. All these changes showed a marked difference between the caput and the cauda.

CONCLUSIONThe polyamine biosynthesis in the hamster epididymis can be affected by DES, a xenoestrogen. DES may probably affect polyamine metabolism in the epididymis by regulating the rate-limiting enzymes involved in the polyamine biosynthesis.

Acetyltransferases ; metabolism ; Animals ; Cricetinae ; Diethylstilbestrol ; pharmacology ; Epididymis ; anatomy & histology ; drug effects ; metabolism ; Male ; Mesocricetus ; Organ Size ; drug effects ; Ornithine Decarboxylase ; metabolism ; Polyamines ; metabolism ; Putrescine ; metabolism ; Spermidine ; analogs & derivatives ; metabolism ; Spermine ; metabolism

The formation of advanced glycation end products (AGEs) has been considered to be a potential causative factor of injury to lens epithelial cells (LECs). Damage of LECs is believed to contribute to cataract formation. The purpose of this study was to investigate the cytotoxic effect of AGEs on LECs both in vitro and in vivo. We examined the accumulation of argpyrimidine, a methylglyoxal-derived AGE, and the expression of apoptosis-related molecules including nuclear factor-kappaB (NF-kappaB), Bax, and Bcl-2 in the human LEC line HLE-B3 and in cataractous lenses of Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. In cataractous lenses from twenty-one-week-old ZDF rats, LEC apoptosis was markedly increased, and the accumulation of argpyrimidine as well as subsequent activation of NF-kappaB in LECs were significantly enhanced. The ratio of Bax to Bcl-2 protein levels was also increased. In addition, the accumulation of argpyrimidine triggered apoptosis in methylglyoxal-treated HLE-B3 cells. However, the presence of pyridoxamine (an AGEs inhibitor) and pyrrolidine dithiocarbamate (a NF-kappaB inhibitor) prevented apoptosis in HLE-B3 cells through the inhibition of argpyrimidine formation and the blockage of NF-kappaB nuclear translocalization, respectively. These results suggest that the cellular accumulation of argpyrimidine in LECs is NF-kappaB-dependent and pro-apoptotic.
Animals ; Apoptosis/*drug effects ; Cell Line ; Epithelial Cells/*cytology/*drug effects ; Glycosylation End Products, Advanced/*pharmacology ; Lens, Crystalline/*cytology ; Male ; Ornithine/*analogs & derivatives/pharmacology ; Pyrimidines/*pharmacology ; Pyruvaldehyde/*chemistry ; Rats