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 Tsukamoto, Hirofumi Makino, Mark A. Lawson

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalMolecular and cellular endocrinology
Volume348
Issue number1
DOIs
Publication statusPublished - Jan 2 2012

Keywords

  • Bone morphogenetic protein
  • Follicle-stimulating hormone (FSH)
  • Gonadotrope
  • Gonadotropin-releasing hormone (GnRH)
  • LβT2 cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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