Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas

Masaya Takeda, Fumio Otsuka, Jiro Suzuki, Masayuki Kishida, Toshio Ogura, Takashi Tamiya, Hirofumi Makino

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48 Citations (Scopus)


Roles of activin/bone morphogenetic protein (BMP) system in the pathogenesis of human pituitary adenoma remain unknown although these factors stimulate follicle-stimulating hormone (FSH) secretion in the normal pituitary. Here we demonstrated that type-I and -II subunit mRNAs of activin/BMP receptors are expressed in Pit-1-negative FSH-producing (FSH-oma) and nonfunctioning pituitary adenomas (NF-oma). Basal levels of serum FSH standardized by luteinizing hormone (LH) were markedly high in FSH-omas in contrast to NF-omas. However, gonadotropin-releasing hormone (GnRH)-induced increment of FSH standardized by that of LH was not changed in FSH-omas, suggesting that imbalanced FSH secretion by FSH-oma is not attributable to GnRH regardless of the expression of GnRH receptor. Although activin βA subunit was detected in neither adenoma, the βB subunit was expressed highly in FSH-omas and, to lesser extent, in NF-omas. As for BMPs, BMP-6 and -7 were detected in NF-omas while BMP-4 and -15 were not detected in either type of adenoma. In the presence of pituitary activin/BMP system, the levels of co-expressing follistatin mRNA in the tumors were reduced in FSH-oma compared with NF-oma, suggesting that endogenous follistatin is involved in FSH overproduction through inhibition of activin/BMP system independently of GnRH.

Original languageEnglish
Pages (from-to)812-818
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - Jul 11 2003


  • Activin
  • Bone morphogenetic protein
  • Follicle-stimulating hormone
  • Follistatin
  • Gonadotropin-releasing hormone
  • Gonadotropinoma
  • Luteinizing hormone
  • Macroadenoma
  • Pituitary adenoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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