The impact of prenatal exposure to a single dose of testosterone on insulin resistance, glucose tolerance and lipid profile of female rat's offspring in adulthood.

PURPOSE: In our previous study, we introduced a rat model of polycystic ovary syndrome (PCOS) induced by prenatal exposure to a single dose of testosterone on embryonic day 20. In the current study, we aimed to investigate whether prenatal exposure to a single dose of testosterone could also induce metabolic disturbances, especially insulin resistance in adulthood (100-110 days of age) and also to make it as an appropriate rat model of PCOS (exhibiting both reproductive and metabolic disturbances with minimum morphological disorders in reproductive system) for further studies in PCOS. METHODS: Pregnant rats in the experimental group were subcutaneously injected with 5 mg free testosterone on the gestational day 20, while controls received only the solvent. Female offspring of both groups, prenatally androgenized (PNA) rats (PCOS models of rats) and controls were examined. RESULTS: Body weight measures showed significant increase in the PNA rats compared to controls on days 30, 45, 60 of age and in adulthood (P < 0.05). PNA rats showed insulin resistance compared to controls. Impaired glucose tolerance was not observed in the PNA rats compared to controls. There were no significant differences in lipid profile between the PNA and control rats (P > 0.05). CONCLUSION: Our study suggests that metabolic disturbances in PCOS and their severity during adult life probably depend on the particular time and levels of prenatal androgen exposure.

The effect of thyroidectomy and propylthiouracil-induced hypothyroidism on insulin secretion in male rats.

Data available on thyroid dysfunction and insulin secretion are inconsistent. The aim of this study was to assess the effect of hypothyroidism on insulin secretion, in vivo and in vitro, in rats. Adult Wistar male rats were divided into 4 groups, the control, the propylthiouracyl (PTU)-treated hypothyroid, the surgically thyroidectomized, and the sham-operated thyroidectomized. After 5 weeks, intravenous glucose tolerance test (IVGTT) was performed and 3 weeks later pancreatic islets were isolated to assess glucose induced insulin secretion and insulin content. Fasting serum glucose and insulin levels did not differ between the groups, but serum glucose concentration during IVGTT in the PTU-induced hypothyroid group was significantly higher as compared to controls, throughout 5-60 min. The serum glucose concentration during IVGTT in the thyroidectomized rats was also significantly higher than in the sham-operated ones, except at 10 and 60 min. The area under the curve of the serum insulin was significantly lower during IVGTT in the PTU-treated (10,010 ± 1,380 pmol/l/60 min) and thyroidectomized (13,930 ± 2,786) groups vs. their comparable groups (19,150 ± 2,110), p<0.01 and (20,650 ± 1,601), p<0.05, respectively. In the PTU-treated, but not in thyroidectomized animals, insulin secretion in response to glucose 8.3 and 16.7 mM was significantly lower than their comparable group. The results show that PTU- and thyroidectomy-induced hypothyroidism leads to impaired glucose tolerance due to reduced glucose stimulated insulin secretion. Islets insulin secretion is positively correlated with serum T3 and T4 concentrations.