Divergent roles of Sirtuin 1 in human granulosa-lutein cells: similarities to hCG.

Sirtuin 1 (SIRT1) is an NAD+ dependent deacetylase that modifies gene expression through histone deacetylation. It also deacetylates non-histone substrates, e.g. tumor suppressor p53, NOS3, HIF1A, NFKB, FOXO3a, PGC-1α, and PPARγ. Consequently, it regulates a wide range of physiological functions including cell cycle control, energy expenditure, oxidative stress response, apoptosis, and aging. SIRT1 is expressed in ovarian granulosa cells (GCs) of various species including humans at different stages of the reproductive cycle. The importance of SIRT1 in female reproduction is supported by the findings that SIRT1-knockout mice exhibit defects in reproductive tissue development. These mice were found to have a thin-walled uterus, small ovaries, with follicles present but no corpora lutea. This review aims to provide state-of-the-art information on SIRT1's mode of action and its roles in human granulosa-lutein cells and GCs from other species where data is available. It also discusses the overlapping actions of SIRT1 and hCG on the production of critical GC-borne factors.