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

TitleFollistatin-like 3 (FSTL3) mediated silencing of transforming growth factor β (TGFβ) signaling is essential for testicular aging and regulating testis size.
Publication TypeJournal Article
Year of Publication2013
AuthorsOldknow KJ, Seebacher J, Goswami T, Villen J, Pitsillides AA, O'Shaughnessy PJ, Gygi SP, Schneyer AL, Mukherjee A
JournalEndocrinology
Volume154
Issue3
Pagination1310-20
Date Published2013 Mar
ISSN1945-7170
KeywordsAging, Animals, Cell Count, Follistatin-Related Proteins, Ligands, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Organ Size, Proteins, Proto-Oncogene Proteins c-akt, Sertoli Cells, Signal Transduction, Sirtuin 1, Spermatogenesis, Testis, Transforming Growth Factor beta
Abstract

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.

DOI10.1210/en.2012-1886
Alternate JournalEndocrinology
PubMed ID23407452