We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.

Objectives: In human medicine, estrogen is applied in prevention and treatment of health problems associated with the menopause. The aim of this study was to examine the effects of chronic estradiol dipropionate (EDP) treatment on thyroid gland structure and function in middle-aged female rats. Methods: At 14 months of age, Wistar rats received 0.625 mg EDP/kg b.w./day intraperitoneally for 2 weeks. The peripheral and central zones of the thyroid were stereologically analyzed and the following morphometric parameters determined: volume density of follicles, follicular epithelium, interstitium and colloid, epithelial height and the index of activation rate. Serum levels of TSH, T4 and T3 were determined by ELISA. Results: EDP treatment led to significant decreases in volume densities of follicles and follicular epithelium, epithelial height and index of activation rate (by 11%, p < 0.05; 23%, p < 0.005; 11%, p < 0.05 and 21%, p < 0.05, respectively) in comparison to control values. Hyperplasia of thyroid follicular cells was noticed in 25% of EDP-treated animals. Serum levels of T4 and T3 were decreased (by 33%, p < 0.005 and 28%, p < 0.001, respectively), but TSH concentration was not significantly different from that of the controls. Conclusion: Chronic estradiol treatment significantly decreased volume density and height of centrally located follicular epithelium, follicular activation index and serum level of total thyroid hormones in middle-aged rats.

Elevated glucocorticoid levels in the gravid female circulation affect a number of endocrine functions in the fetuses and neonates. The aim of this study was to examine the effects of maternal dexamethasone (Dx) administration during late pregnancy on the ovaries of neonatal offspring. On the 16th day of pregnancy, experimental dams received subcutaneously 1.0 mg Dx/kg b.w., followed by 0.5 mg Dx/kg b.w./day on the 17th and 18th days of gestation. The control gravid females received the same volume of saline vehicle. Left ovaries from 5-day-old female pups were stereologically analyzed. The ovary volumes were estimated using Cavalieri's principle. The number of healthy and atretic primordial and primary follicles was estimated using a fractionator-physical dissector method. The number of secondary follicles was determined by exact counts of every fourth section encompassing whole cross-sections of the ovary. The ovary volume was significantly decreased (by 44.4%; P < 0.05) in the group of female pups from Dx-treated mothers comparing to the controls. The numbers of healthy primordial and atretic follicles were 38.8% (P < 0.05) and 50.9% (P < 0.05), respectively, reduced in the ovaries of pups from the Dx-treated mothers, when compared with the control values. There were 53.4% (P < 0.05) fewer healthy primary and 41.8% (P < 0.05) fewer healthy secondary follicles as well. The numbers of atretic primary and secondary follicles were reduced by 60.0% (P < 0.05) and 61.7% (P < 0.05), respectively. It can be concluded that fetal exposure to glucocorticoids decreased the pool of non-growing follicles in the neonatal ovary, whereas the processes of folliculogenesis and atresia remained unaffected.