Changes in peroxisome proliferator-activated receptor gamma-regulated gene expression and inhibin/activin-follistatin system gene expression in rat testis after an administration of di-n-butyl phthalate.
Changes in gene expression regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) and in gene expression related to the inhibin/activin-follistatin system in the rat testis induced by a single oral administration of di-n-butyl phthalate (DBP) (8.6 mmol/kg) were examined and compared with those in the control rats using reverse-transcriptase polymerase chain reaction (RT-PCR). The increase in cytochrome P450 4A1 mRNA, which is regulated by PPARalpha, was significant, but not so profound as the increase of P450 4A1 mRNA in the liver. In contrast, a remarkable increase in the mRNA level of plasminogen activator inhibitor-1 (PAI-1) was found in the testis, suggesting the activation of PPARgamma. The substantial increase in PAI-1 may be related to the disruption of spermatogenesis. On the other hand, significant suppression of the mRNA level of inhibin beta(B) and elevation in the mRNA level of follistatin, an activin-binding protein, were observed after the DBP-administration. Activin B, a homodimer of inhibin beta(B), is known to stimulate spermatogonial proliferation. The present results suggest that the suppression of spermatogenesis resulting from the changes in the expression of genes involved in the inhibin/activin-follistatin system is one of the mechanisms of the testicular atrophy induced by DBP.
Kobayashi
Tetsu
T
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. kobayash@nihs.go.jp
Niimi
Shingo
S
Kawanishi
Toru
T
Fukuoka
Masamichi
M
Hayakawa
Takao
T
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D003993:Dibutyl Phthalate / Q000633:toxicity*; D038681:Follistatin / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007265:Inhibins / Q000096:biosynthesis / Q000235:genetics*; D007473:Ion Channels; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000071246:Uncoupling Protein 2
C465387:Cyp4a1protein, rat; D038681:Follistatin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000071246:Uncoupling Protein 2; D003993:Dibutyl Phthalate; D007265:Inhibins; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4