Di (n-butyl) phthalate inhibits testosterone synthesis through a glucocorticoid-mediated pathway in rats.
The present study focused on investigating whether the inhibitory effect of di (n-butyl) phthalate (DBP) on testosterone (T) biosynthesis was mediated by the glucocorticoid (GC) pathway in prepubertal male rats and T production after the exposure to DBP ceased. Prepubertal male rats were administered DBP in corn oil orally at 0, 250, 500, 1000, and 2000 mg/kg daily for 30 days. Serum T and GC were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The responses, including glucocorticoid receptor (GR), type I 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), and steroidogenesis acute regulatory protein (StAR) in the testes tissues, were determined by Western blotting and reverse transcriptase PCR. DBP exposure resulted in testicular toxicity, such as seminiferous tubule degeneration and a decrease in the number of spermatogenic cells. T was decreased and GC was increased in a DBP concentration-dependent manner in the exposure group. The expression of GR and 11beta-HSD1 was significantly increased, with an associated decrease in expression of StAR. Neither the expression of the GR nor 11beta-HSD1 and StAR were statistically significantly different in the postexposure group compared with the control. However, the weight and morphology of the testes did not recover in the postexposure group. These data suggest that DBP inhibits testosterone production through a GC-mediated pathway in prepubertal male rats, and after exposure to DBP ceases, testosterone biosynthesis returns.
Xiao-feng
Zhang
Z
Division of Toxicology, Public Health College, Harbin Medical University, Nangang District, Harbin, Heilongjiang Province, China.
Nai-qiang
Qu
Q
Jing
Zheng
Z
Zi
Li
L
Yang
Zhang
Z
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003993:Dibutyl Phthalate / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010968:Plasticizers / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
D005938:Glucocorticoids; D010750:Phosphoproteins; D010968:Plasticizers; D011965:Receptors, Glucocorticoid; D000098682:Steroidogenic Acute Regulatory Protein; D003993:Dibutyl Phthalate; D013739:Testosterone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1