Heat stress upregulates aromatases expression through nuclear DAX-1 deficiency in R2C Leydig tumor cells.

An appropriate balance between testicular testosterone and estradiol is required for spermatogenesis. Excess estradiol is often identified in the semen and serum of infertile men; however, the mechanisms behind this observation remain unclear. This study indicates the relationship between heat stress and aromatase synthesis in Leydig cells. We used R2C rat Leydig tumor cells, which can synthesize both testosterone and estradiol. Aromatase transcription was regulated by the PⅡ promoter with or without heat stress. Heat stress at 40 °C increased aromatase expression and decreased testosterone to estradiol ratio and nuclear DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1), which is a suppressor of steroidogenic factor 1 (SF-1). Leptomycin B and KPT-185, a nuclear export inhibitor, prevented nuclear DAX-1 deficiency induced by heat stress and inhibited aromatase transcription. These results indicate that heat stress interferes with DAX-1-SF-1 interaction and induces SF-1-dependent aromatase transcription.

[The effects of chronic alcohol exposure on progression of liver injury in spontaneously hypertensive rats; preliminary study].

The association between alcohol intake and blood pressure is well known, and our previous studies indicate that the stimulus of sympathetic nervous system induce the progression of liver injury. In this study, we examined the effects of chronic ethanol treatment on the progression of liver injury using the spontaneously hypertensive rat (SHR). The advantage of using the present strain is to possess sympathetic facilitation without any treatment. Normotensive Wistar-Kyoto rat (WKY) was used as control. 7-week-old male rats were pair-fed with either ethanol- or control-liquid-diet for 49 days and divided into four groups: control liquid-diet-fed WKY and SHR, continuous ethanol liquid diet-fed WKY and SHR. Plasma alanine aminotransferase (ALT) levels, and histological analyses based on Hematoxylin-Eosin (H-E), Oil red O and Sirius red stains of the liver sections were used to assess alcohol-induced liver injury. Chronic ethanol treatment induced the increases in plasma ALT, the accumulation of fatty droplets within hepatocytes and pericellular hepatic fibrosis, particularly in SHR. Between the control group rats of SHR and WKY, SHR showed the increases in accumulation of fatty droplets and pericellular hepatic fibrosis. No significant inflammatory cell infiltration was shown in all groups. These results suggested that chronic ethanol treatment in SHR could induce the more severe liver injuries when compared with WKY. In conclusion, chronic alcohol intake in rats with hypertension could deteriorate the ethanol-induced liver injury via the sympathetic overactivity.