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.
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.
Minegishi
Takashi
T
Department of Obstetrics and Gynecology School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan. tminegis@showa.gunma-u.ac.jp
Hirakawa
Takashi
T
Abe
Kazuko
K
Kishi
Hiroshi
H
Miyamoto
Kaoru
K
D000818:Animals; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D011974:Receptors, LH; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone