PubMed · 10346736
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1998. The TEC experience.. https://pubmed.ncbi.nlm.nih.gov/10346736/
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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.
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Involvement of androgens in vitellogenin (VTG) synthesis was investigated using the primary hepatocyte cultures of tilapia, Oreochromis mossambicus. Concentration of VTG in the medium was assessed by enzyme-linked immunosorbent assay. When the hepatocytes of females were treated with testosterone (T), 17 alpha-methyltestosterone (MT) and 5 alpha-dihydrotestosterone (DHT), VTG concentration in the medium slightly increased or maintained. DHT, but not T and MT, increased VTG in the medium of male hepatocyte cultures. However, VTG production in the male hepatocytes, which were previously treated with estradiol-17 beta (E(2)), maintained high level by treatment of T. Similarly, co-treatment of E(2) and the androgens to the male hepatocytes enhanced VTG concentration in the medium. These results suggest that the androgens have some roles in VTG synthesis in the hepatocytes. Tamoxifen, a nonsteroidal antiestrogen, reduced VTG synthesis by the androgens. On the other hand, co-treatment of T and fadrozole, an aromatase inhibitor, failed to inhibit the effect of VTG synthesis by T alone. Analysis with RT-PCR did not demonstrate expression of the brain and the ovarian types of aromatase mRNA in the liver. These results suggest that the possibility of local aromatization of the androgens in the tilapia liver is low and that androgens bind estrogen receptor and, consequently, exert estrogenic action. Treatment of cyproterone acetate, an antiandrogen reagent, increased production of VTG with DHT. Involvement of androgens might not be ignored in regulation of VTG synthesis in the liver.