Fetal pituitary gonadotropin as an initial target of dioxin in its impairment of cholesterol transportation and steroidogenesis in rats

Junpei Mutoh, Junko Taketoh, Kazuharu Okamura, Tetsushi Kagawa, Takumi Ishida, Yuji Ishii, Hideyuki Yamada

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Reproductive and developmental disorders are the most sensitive toxic effects caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is thought to produce many, if not all, of these toxic effects by impairing steroidogenesis and/or steroid action during the prenatal or early postnatal stages. However, the mechanism of the antisex steroid effect of TCDD is not well understood. This study revealed that steroidogenic acute-regulatory protein (StAR), a key transporter of cholesterol for steroidogenesis, in the testes of fetal rats are down-regulated by maternal exposure to TCDD. It was also shown that many mRNAs of steroidogenetic enzymes, including cytochromes P450 11A1, 17, and 11B1 and 3β-hydroxysteroid dehydrogenase, are reduced in fetuses of TCDD-treated dams in a testis-specific manner. The same was also observed for the expression of estrogen-α receptors and androgen receptors. Whereas StAR expression was not affected by TCDD in cultured fetal testis, the fetal serum content of LH, a pituitary regulator of StAR, was significantly reduced by TCDD. In agreement with this, pituitary expression of LHβ subunit mRNA in fetuses was reduced by maternal exposure to TCDD, whereas the α-subunit remained unchanged. The reduction in LHβ is suggested to occur by a mechanism different from the reduction in the GnRH level. Direct supply of exogenous gonadotropin to TCDD-exposed fetuses completely abolished the reduction of StAR expression. Taken together, these results demonstrate that TCDD impairs steroidogenesis in the fetus by targeting pituitary gonadotropins.

Original languageEnglish
Pages (from-to)927-936
Number of pages10
JournalEndocrinology
Volume147
Issue number2
DOIs
Publication statusPublished - Feb 2006

All Science Journal Classification (ASJC) codes

  • Endocrinology

Fingerprint Dive into the research topics of 'Fetal pituitary gonadotropin as an initial target of dioxin in its impairment of cholesterol transportation and steroidogenesis in rats'. Together they form a unique fingerprint.

Cite this