Effects of flutamide in the rat testis on the expression of occludin, an integral member of the tight junctions.
In an effort to uncover the gonadal impairment by the antiandrogen flutamide (FM) in males, the effect of subacute administration of FM on the expression of tight junction (TJ) genes that build the blood-testis barrier (BTB) was investigated in adult rat testis. At 13 weeks old of age male rats were given vehicle (corn oil) or FM (25 mg/kg per day, in corn oil) orally for 6 days. At 8 days (D8) after the first dose, testicular expression of the occludin, claudin-1, and -11 was analyzed by semiquantitative RT-PCR. The testicular weight of the FM-treated rats on D8 was a little but significantly higher than in the control group. On D8 the expression of occludin in the FM-treated animals was significantly decreased but claudin-1 and -11 were not altered significantly. Because FM administration inhibits germ cell differentiation, it is likely that the down-regulated occludin expression in FM-rat testes may be attributed to the alteration in the paracrine interaction between Sertoli cells and germ cells in testis. It also emphasized that FM might have differentially affected the transcription of TJ genes in Sertoli cells building the BTB. These findings provide a rationale for a number of observations on the gonadal impairment by FM in males and suggest that FM is potentially harmful to spermatogenesis by alteration of the BTB.
Gye
Myung Chan
MC
Department of Life Science, College of Natural Sciences, Hanyang University, 133-791, Seoul, South Korea. mcgye@hanyang.ac.kr
Ohsako
Seiichiroh
S
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D062445:Claudin-1; D057167:Claudins; D015536:Down-Regulation / Q000187:drug effects; D005485:Flutamide / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D062793:Occludin; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*
D000726:Androgen Antagonists; D062445:Claudin-1; D057167:Claudins; C568114:Cldn1 protein, rat; C492353:Cldn11 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D062793:Occludin; C568987:Ocln protein, rat; D012333:RNA, Messenger; D005485:Flutamide