Search

Emerging evidence suggests that the glucocorticoid and estradiol are important for Leydig cell steroidogenesis and are regulated via aromatase for estradiol production and 11beta-HSD for oxidatively inactivating glucocorticoid. Although it is known that corticosterone deficiency impaired Leydig cell steroidogenesis, its effect on the expression of Leydig cell 11beta-HSD type I and aromatase are yet to be recognized. Following metyrapone-induced corticosterone deficiency, serum corticosterone and testosterone levels decrease, whereas serum estradiol remains unaltered. 11beta-HSD type I mRNA and its activity was decreased by corticosterone deficiency, whereas the activity and mRNA of aromatase remains unaltered. Simultaneous administration of corticosterone prevented its deficiency-induced changes of 11beta-HSD type I in Leydig cells. Our results show that metyrapone-induced corticosterone deficiency impairs Leydig cell 11beta-HSD enzyme activity and 11beta-HSD type I mRNA expression, and the Leydig cells need to maintain their intracellular concentration of corticosterone for a normal function.

The habitual consumption of even moderate quantities of alcoholic beverages is clearly associated with reduced bone mass, increased prevalence of skeletal fracture and also it is the major risk factor for the development of secondary osteoporosis. The present in vitro study was designed to determine the dose response effects of ethanol on osteoblast-like human osteosarcoma cells (SaOS-2) proliferation, differentiation, mineralization and cyto-toxicity. SaOS-2 cells were plated in 48 and 6 well culture plates and exposed to different concentrations of ethanol (1, 10, 100, 200 and 300 mM) for 24, 48 and 72 h. At the end of incubation, proliferation of cells was studied using crystal violet Bioassay. The cell lysate was utilized to determine ALP activity and conditioned media were used to measure LDH activity. Histochemical localization of ALP and mineralized nodules were studied from cells treated with ethanol (10 and 100 mM) for 21 days. At higher doses, there was a significant reduction in cell number, whereas at lower doses there were variable effects. In 24 h treatment, the higher doses showed a significant increase in ALP activity, whereas 48 and 72 h treatments showed an opposite trend. Ethanol treatment caused a dose- and time-dependent increase in LDH activity. Ethanol treatment altered the quality of mineralization at 10 mM dose whereas completely inhibited mineralization at 100 mM dose, despite the presence of serum. In conclusion, the toxic effect of ethanol is reflected on cell proliferation, differentiation and mineralization even at low doses and at extended treatment duration.

Male osteoporosis is an increasingly important health problem worldwide. Though androgen deficiency leads to bone loss in men, information on the relative contribution of aromatizable and non-aromatizable androgens in maintaining bone mineral density (BMD) and the mechanisms involved are unclear. This cross-sectional study was designed to explore the same. Hundred osteoporotic men with age matched normal were studied for serum levels of sex steroids, PTH, IGF system components, cytokines and bone turnover markers. Our findings show that serum DHT, IGF-I, IGF-II and IGFBP-3 levels were significantly decreased while IL-1beta and bone turnover markers were significantly increased in osteoporotic men compared to normal. Pearson correlation analysis revealed that serum DHT, IGF-I, IGF-II and IGFBP-3 levels were positively and strongly correlated with BMD, while serum IL-1beta levels were negatively correlated with BMD. Serum PTH, testosterone, estradiol, IGFBP-4, TNF-alpha, IL-4 and IFN-gamma levels were similar between the two groups. We observed that DHT levels significantly declined with age. However, the significant difference in DHT between the osteoporotic and normal groups is the same regardless of age. A multiple regression model adjusted for age demonstrated that DHT/BMD association is fairly stronger among those with osteoporosis than the normal. Our findings for the first time point out that DHT is an important determinant of BMD in men. Most importantly, the strong positive correlation of serum DHT with BMD offers new perspectives in understanding the role of non-aromatizable androgen in regulating bone metabolism in men, and might serve as a potential clinical marker in the diagnosis of male osteoporosis.