1.Change in hair growth-related gene expression profile in human isolated hair follicles induced by 5-alpha reductase inhibitors - dutasteride and finasteride - in the presence of testosterone.
Toshiki HATANAKA ; Zrinka LULIC ; Tim MEFO ; Cath BOOTH ; Elliott HARRISON ; Gary ONG
Singapore medical journal 2022;63(9):552-558
2.Inhibitory effect of dutasteride on the expressions of epididymal Claudin1 and β-catenin in male rats.
Shu-wu XIE ; Li-juan QU ; Xian-ying ZHOU ; Jie-yun ZHOU ; Guo-ting LI ; Ji-hong BI ; Xiang-jie GUO ; Zhao LI ; Lin CAO ; Yan ZHU
National Journal of Andrology 2015;21(1):17-22
OBJECTIVETo explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.
METHODSSixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.
RESULTSDutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).
CONCLUSIONDutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.
Animals ; Azasteroids ; pharmacology ; Claudin-1 ; metabolism ; Dihydrotestosterone ; blood ; Dutasteride ; Epididymis ; drug effects ; metabolism ; Female ; Fertility ; drug effects ; Humans ; Intercellular Junctions ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testosterone ; blood ; Urological Agents ; pharmacology ; beta Catenin ; metabolism
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