Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells

Masaya Takeda, Fumio Otsuka, Hiroaki Takahashi, Kenichi Inagaki, Tomoko Miyoshi, Naoko Yamauchi, Hirofumi Makino, Mark A. Lawson


15 被引用数 (Scopus)


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 LβT2 cells. In LβT2 cells, BMP-6 and BMP-7 increased mouse FSHβ-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 FSHβ transcription regulation. Notably, BMP-6, but not BMP-7, enhanced GnRH-induced FSHβ-promoter activity in LβT2 cells. Since GnRH stimulated MAPK phosphorylation in LβT2 cells, a functional link between MAPK and FSHβ transcription was examined. Inhibition of the ERK pathway, but not that of p38 or SAPK/JNK signaling, suppressed GnRH-induced FSHβ transcription, suggesting that ERK is functionally involved in GnRH-induced FSHβ transcription. Co-treatment with BMP-7, but not with BMP-6, suppressed GnRH-induced MAPK phosphorylation in LβT2 cells. Thus, the difference between BMP-6 and BMP-7 in enhancing GnRH-induced FSHβ 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.

ジャーナルMolecular and cellular endocrinology
出版ステータスPublished - 1月 2 2012

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 内分泌学


「Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。