Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor β (TGFβ) signaling is essential for testicular aging and regulating testis size

Endocrinology. 2013 Mar;154(3):1310-20. doi: 10.1210/en.2012-1886. Epub 2013 Feb 13.


Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGFβ ligands such as activin. The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood. The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression. These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function. The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis. This demonstrates a cross-talk between TGFβ ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging. The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression.

Publication types

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

MeSH terms

  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Cell Count
  • Follistatin-Related Proteins / deficiency
  • Follistatin-Related Proteins / genetics
  • Follistatin-Related Proteins / physiology*
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size / genetics
  • Organ Size / physiology
  • Proteins / genetics
  • Proteins / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sertoli Cells / pathology
  • Signal Transduction
  • Sirtuin 1 / metabolism
  • Spermatogenesis / genetics
  • Spermatogenesis / physiology
  • Testis / pathology
  • Testis / physiology*
  • Transforming Growth Factor beta / physiology*


  • Follistatin-Related Proteins
  • Fstl3 protein, mouse
  • Ligands
  • Proteins
  • Transforming Growth Factor beta
  • Proto-Oncogene Proteins c-akt
  • Sirt1 protein, mouse
  • Sirtuin 1