Document Detail


Suppression of fetal testicular cytochrome P450 17 by maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: a mechanism involving an initial effect on gonadotropin synthesis in the pituitary.
MedLine Citation:
PMID:  17291543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the fetal expression of testicular cytochrome P450 17 (CYP17), one of the enzymes necessary for sex steroid synthesis, was studied in Wistar rats. Fetal testicular CYP17 exhibited reduced mRNA and protein levels following exposure of the dams at gestational day 15 to 1 microg/kg TCDD. In support of this, CYP17 activity catalyzed by fetal testis homogenate was also reduced by maternal exposure to TCDD. The reduction in CYP17 expression seemed to be specific for fetal stages, because 7 day-old pups born from TCDD-treated dams did not exhibit any reduction in CYP17. In sharp contrast to the in vivo observations, TCDD failed to reduce CYP17 expression in cultured fetal testis, although CYP17 could be induced by activating cAMP-dependent signaling. To assess the role of pituitary luteinizing hormone (LH) on TCDD-induced reduction in fetal testicular CYP17, a further investigation was performed to examine whether the direct injection of LH into fetuses restores the altered CYP17 expression. The results showed that in utero injection of equine chorionic gonadotropin, an LH-mimicking hormone, completely abolishes the TCDD-produced reduction in fetal CYP17. However, neither the alpha- nor beta-subunits of LH in cultured fetal pituitary was reduced by TCDD. These results suggest that 1) maternal exposure to TCDD impairs the expression of testicular CYP17 in a fetal stage-specific manner; 2) this effect is due, at least partially, to a TCDD-produced reduction in circulating LH; and 3) TCDD exerts such an effect by affecting the upstream mechanism regulating the pituitary synthesis of LH.
Authors:
Junko Taketoh; Junpei Mutoh; Tomoki Takeda; Tadashi Ogishima; Shuso Takeda; Yuji Ishii; Takumi Ishida; Hideyuki Yamada
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-18
Journal Detail:
Title:  Life sciences     Volume:  80     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-05     Completed Date:  2007-04-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1259-67     Citation Subset:  IM    
Affiliation:
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclic AMP / biosynthesis
Cytochrome P-450 CYP1A1 / genetics,  metabolism
Environmental Pollutants / toxicity*
Female
Gene Expression / drug effects
Gonadotropins, Equine / pharmacology
Injections
Liver / drug effects,  enzymology
Luteinizing Hormone / biosynthesis*
Male
Maternal Exposure
Organ Culture Techniques
Pituitary Gland / drug effects*,  embryology,  metabolism
Pregnancy
Prenatal Exposure Delayed Effects
RNA, Messenger / metabolism
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*,  biosynthesis,  genetics
Testis / embryology,  enzymology*
Tetrachlorodibenzodioxin / toxicity*
Chemical
Reg. No./Substance:
0/Environmental Pollutants; 0/Gonadotropins, Equine; 0/RNA, Messenger; 1746-01-6/Tetrachlorodibenzodioxin; 60-92-4/Cyclic AMP; 9002-67-9/Luteinizing Hormone; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.99.9/Steroid 17-alpha-Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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