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  • Title: Effect of insulin-like growth factor-1 and 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of luteinizing hormone receptors in cultured granulosa cells.
    Author: Minegishi T, Hirakawa T, Abe K, Kishi H, Miyamoto K.
    Journal: Environ Sci; 2004; 11(1):57-71. PubMed ID: 15746889.
    Abstract:
    In this study, we attempted to assess the effects of insulin-like growth factor-1 (IGF-1) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on follicle-stimulating hormone (FSH)-induced luteinizing hormone (LH) receptor expression in rat granulosa cells to understand the effects of these factors on normal reproductive function. Treatment with FSH, as expected, produced a substantial increase in LH receptor mRNA expression level, and cotreatment with an increasing concentration of IGF-1 resulted in a dose-dependent increase in FSH-induced LH receptor mRNA expression level. On the other hand, the cotreatment with FSH and TCDD (10 pM) resulted in a significant decrease in LH receptor mRNA expression level after 24 h. The decay curves for the LH receptor mRNA transcript showed a significant increase in half-life after the addition of IGF-1 and a significant decrease after the addition of TCDD. These data suggest a possible role for changes in LH receptor mRNA stability in the IGF-1- and TCDD-induced regulation of the LH receptor in rat granulosa cells. The rates of LH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, did not increase after the addition of IGF-1, but decreased after the addition of TCDD. The data for IGF-1 indicate that the interface between circulating hormones and paracrine/autocrine systems could provide an important mechanism for amplifying the effects of gonadotropin hormones at the local level. In addition, the endocrine-disrupting effects of TCDD are, at least in part, caused by the direct action on the LH receptor expression on granulosa cells.
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