Bone morphogenetic protein signaling transcription factor (SMAD) function in granulosa cells

Mol Cell Endocrinol. 2012 Jun 5;356(1-2):40-7. doi: 10.1016/j.mce.2011.06.021. Epub 2011 Jul 7.


The transforming growth factor β (TGFβ) family of proteins are key regulators of growth and differentiation. Members of this family, including multiple TGFβs, activins, bone morphogenetic proteins (BMPs), and growth and differentiation factor 9 (GDF9), are expressed from oocytes or their associated follicular somatic cells (granulosa and thecal cells) with cell-type and stage-dependent specificity. Granulosa cells are the target cells for many of these ligands. Granulosa cell-specific knockout mice for all of the receptor-regulated SMADs, as well as the common regulatory SMAD4, have recently been generated and highlight the importance of this family in most stages of folliculogenesis. These models have also uncovered a novel role for the BMPs in suppression of granulosa cell tumor development and metastasis. This review summarizes the phenotypes of these mouse models and their contribution to our understanding of the complexity of BMP function during follicle development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / physiology*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Female
  • Gene Expression Regulation
  • Granulosa Cell Tumor / genetics
  • Granulosa Cell Tumor / metabolism
  • Granulosa Cells / metabolism*
  • Granulosa Cells / physiology
  • Humans
  • Ovarian Follicle / pathology
  • Ovarian Follicle / physiology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Signal Transduction
  • Smad Proteins / genetics
  • Smad Proteins / metabolism
  • Smad Proteins / physiology*


  • Bone Morphogenetic Proteins
  • Smad Proteins