BMP-6 modulates somatostatin effects on luteinizing hormone production by gonadrotrope cells

Kishio Toma, Fumio Otsuka, Kohei Oguni, Tomohiro Terasaka, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Hirofumi Makino

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The effects of somatostatin analogs and roles of BMP-6 in the regulation of luteinizing hormone (LH) secretion were investigated using mouse gonadotrope LβT2 cells. LH mRNA expression and LH secretion induced by GnRH were suppressed by treatments with somatostatin analogs, including octreotide and pasireotide, in LβT2 cells. Of note, the inhibitory effects of somatostatin analogs on LH secretion were enhanced by the action of BMP-6. BMP-6 increased the expression levels of somatostatin receptor (SSTR)5, suggesting that BMP-6 upregulates SSTR activity that leads to reduction of GnRH-induced LH secretion. In addition, GnRH-induced phosphorylation of MAPKs including ERK, but not P38 or SAPK, was suppressed by pasireotide in the presence of BMP-6. Given that each inhibitor of ERK, JNK or P38 signaling suppressed GnRH-induced LH transcription, MAPKs are individually involved in the induction of LH production by LβT2 cells. Somatostatin analogs also impaired BMP-6-induced Smad1/5/8 phosphorylation by suppressing BMPRs and augmenting Smad6/7 expression. Collectively, the results indicate that somatostatin analogs have dual effects on the modulation of GnRH-induced MAPK signaling and BMP activity. The pituitary BMP system may play a regulatory role in GnRH-induced LH secretion by tuning the responsiveness to somatostatin analogs in gonadotrope cells.

Original languageEnglish
Pages (from-to)96-101
Number of pages6
JournalPeptides
Volume76
DOIs
Publication statusPublished - Feb 1 2016

Keywords

  • Bone morphogenetic protein
  • Gonadotrope
  • Gonadotropin-releasing hormone
  • Luteinizing hormone
  • Somatostatin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'BMP-6 modulates somatostatin effects on luteinizing hormone production by gonadrotrope cells'. Together they form a unique fingerprint.

Cite this