| First Author | Takeda M | Year | 2012 |
| Journal | Mol Cell Endocrinol | Volume | 348 |
| Issue | 1 | Pages | 147-54 |
| PubMed ID | 21846488 | Mgi Jnum | J:184107 |
| Mgi Id | MGI:5320261 | Doi | 10.1016/j.mce.2011.08.001 |
| Citation | Takeda M, et al. (2012) Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LbetaT2 gonadotrope cells. Mol Cell Endocrinol 348(1):147-54 |
| abstractText | It is known that bone morphogenetic proteins (BMPs) regulate gonadotropin transcription and production by pituitary gonadotrope cells. However, the role of BMPs in gonadotropin-releasing hormone (GnRH)-induced FSH production remains uncertain. Here, we describe a functional link between BMP-6 and BMP-7 signals and FSH transcriptional activity induced by GnRH using mouse gonadotrope LbetaT2 cells. In LbetaT2 cells, BMP-6 and BMP-7 increased mouse FSHbeta-promoter activity in a concentration-dependent manner. The induction by BMP-6 and BMP-7 was inhibited by treatment with extracellular domains of ActRII but not BMPRII. These findings suggest that the type II receptor ActRII participates in BMP-induced FSHbeta transcription regulation. Notably, BMP-6, but not BMP-7, enhanced GnRH-induced FSHbeta-promoter activity in LbetaT2 cells. Since GnRH stimulated MAPK phosphorylation in LbetaT2 cells, a functional link between MAPK and FSHbeta transcription was examined. Inhibition of the ERK pathway, but not that of p38 or SAPK/JNK signaling, suppressed GnRH-induced FSHbeta transcription, suggesting that ERK is functionally involved in GnRH-induced FSHbeta transcription. Co-treatment with BMP-7, but not with BMP-6, suppressed GnRH-induced MAPK phosphorylation in LbetaT2 cells. Thus, the difference between BMP-6 and BMP-7 in enhancing GnRH-induced FSHbeta transcription may be due to the differential effects of BMP ligands on GnRH-induced ERK signaling. On the other hand, GnRH reduced Smad1/5/8 phosphorylation but increased Smad6/7 expression. These findings imply the presence of a functional link between GnRH action, MAPK signaling and the BMP system in pituitary gonadotropes for fine-tuning of FSH gene expression. |
