Testicular cytochrome P450scc and LHR as possible targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the mouse.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in adult animals has been reported to perturb the regulation of steroidogenesis in the testis, possibly by arylhydrocarbon receptor (AhR). To clarify how AhR is involved in the testicular steroidogenesis, we carried out comparative experiments using wild-type and AhR-null male mice that were intraperitoneally administered TCDD. The TCDD administration to wild-type mice showed significant reduction of P450scc and LHR in the testis, whereas the levels in the AhR-null mouse testis were unchanged. To compare anti-androgenic properties on hypothalamo-pituitary-gonadal (HPG) axis, estradiol-3-benzoate (EB), a synthetic estrogen agonist, was administered to mice, the expression of the LHalpha/FSHalpha, LHbeta, FSHbeta and GnRHR genes was severely impaired in the pituitary gland, in contrast to no observed effects in the TCDD-treated mice. In addition, the expression of the LHR gene was increased in the testis of the EB-treated mice. These observations suggest that the target of TCDD is different from that of EB on HPG axis and that TCDD treatment suppresses the P450scc and LHR genes in the testis in an AhR-dependent manner.
Fukuzawa
Noriho H
NH
Molecular and Cellular Toxicology Section, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
Ohsako
Seiichiroh
S
Wu
Qing
Q
Sakaue
Motoharu
M
Fujii-Kuriyama
Yoshiaki
Y
Baba
Tadashi
T
Tohyama
Chiharu
C
D000311:Adrenal Glands / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000032:analysis / Q000378:metabolism
D037201:Follicle Stimulating Hormone, beta Subunit; D015292:Glycoprotein Hormones, alpha Subunit; D037101:Luteinizing Hormone, beta Subunit; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011974:Receptors, LH; D011966:Receptors, LHRH; C074283:estradiol 3-benzoate; D013739:Testosterone; D004958:Estradiol; D002786:Cholesterol Side-Chain Cleavage Enzyme