| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2022927 | Regulatory Peptides | 2009 | 7 Pages |
Follistatin regulates FSHβ gene expression by binding to and bioneutralizing activin effects. In this study, we found that thyrotropin-releasing hormone (TRH) increased follistatin gene expression in pituitary somatolactotroph GH3 cells. Treatment of GH3 with 100 nM TRH significantly increased follistatin mRNA expression as determined by real time PCR. TRH-induced follistatin expression was significantly abrogated in the presence of MEK inhibitor, U0126. Overexpression of constitutive active MEKK in GH3 cells dramatically increased follistatin expressions. Transfection of GH3 cells with follistatin siRNA reduced endogenous follistatin mRNA expression, but failed to modulate prolactin promoter activity. Prolactin mRNA levels were not affected by increasing the dose of follistatin, and TRH-induced prolactin promoter activity was not modulated in the presence of follistatin. In other experiments using pituitary gonadotroph LβT2 cells, activin increased FSHβ promoter activity and mRNA expression, and follistatin completely inhibited this activin-increased FSHβ gene expression. Treatment of GH3 cells with activin reduced the basal activity of prolactin promoter and follistatin prevented this effect. GH3 cells were co-cultured with LβT2 cells, which had been transfected with FSHβ promoter-linked luciferase vectors and treated with activin in the presence of TRH. Activin-induced FSHβ promoter activity was completely inhibited in the presence of TRH. In addition to that, FSHβ mRNA was not detected from LβT2 cells which were co-cultured with GH3 cells. Our current results suggest the possibility that TRH increases follistatin gene expression in prolactin-producing cells in association with ERK pathways. Somatolactotroph-derived follistatin affects gonadotrophs by countering activin-induced FSHβ gene expression in a paracrine fashion.
