PURPOSE: The present study was performed to evaluate the effects of tributyltin acetate(TBTA) on mouse testes. The effects of TBTA on mammalian reproduction are not well known. MATERIALS AND METHODS: Three-week-old male mice(ICR strain) were orally administered TBTA at doses of 0 (control vehicle, CV), 25(T25), 50(T50), and 100 mg/kg(T100). Serum and intratesticular concentrations of testosterone and estradiol were determined by conventional radioimmunoassays. RT-PCR analysis was also performed. RESULTS: Transcriptional activity of 3-hydroxysteroid dehydrogenase (3beta-HSD), 17-hydroxysteroid dehydrogenase(17 beta-HSD) and cytochrome P450 17alpha-hydroxylase/C17,20 lyase(P450 (17 alpha)) were decreased by treatment. whereas mRNA levels of P450 aromatase were unaffected. In addition, TBTA significantly decreased serum testosterone levels in T100, while estradiol levels were not affected significantly. CONCLUSIONS: Administration of TBTA decreases testosterone level in testes, and this effect might be due to the alteration of mRNA levels of steroidogenic enzymes. Taken together, these findings suggest that TBTA, impairs testicular functions in a dose-dependent manner. The present results can be used as basic data in the study of TBTA action on gonads.
Animals ; Aromatase ; Cytochrome P-450 Enzyme System ; Estradiol ; Gonads ; Humans ; Male ; Mice* ; Oxidoreductases ; Radioimmunoassay ; Reproduction ; RNA, Messenger ; Testis* ; Testosterone

No abstract available.
Apoptosis* ; Azoospermia* ; Humans* ; Mass Spectrometry* ; Testis*

PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.
Adiponectin/metabolism ; Adiposity/drug effects ; Animals ; Cell Proliferation/drug effects ; Diabetes Mellitus, Type 2/diet therapy/*drug therapy ; Eating/*drug effects ; Glucose Intolerance/diet therapy/*drug therapy ; Insulin Resistance ; Insulin-Secreting Cells/*drug effects/pathology ; Male ; Piperidines/adverse effects/*therapeutic use ; Pyrazoles/adverse effects/*therapeutic use ; Rats ; Rats, Inbred OLETF ; Receptor, Cannabinoid, CB1/physiology ; Thiazolidinediones/*therapeutic use