NCBI Summary:
This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce 2 subunits, large and small, that dimerize to form the active enzyme. The precursor of this caspase can be cleaved by caspase 3 and 10. It has been shown to be activated upon cell death stimuli and induce apoptosis. Alternative splicing of this gene results in 4 transcript variants, which encode 3 distinct isoforms.
General function
Apoptosis
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Follicle atresia
Comment
Expression regulated by
LH
Comment
Apoptosis causes the elimination of ovarian germ cells and the atretic degeneration of ovarian follicles. Yacobi K, et al 2004 have used cultured rat preovulatory follicles to examine the regulation of effector caspase-3 and -7 in follicles undergoing apoptosis in the presence or absence of gonadotropins or IGF-I. Culturing follicles in the presence or absence of serum resulted in the induction of apoptosis of granulosa cells (GC), which was accompanied by effector caspase activation. Surprisingly, the addition of the survival factors LH or FSH, but not IGF-I, further increased caspase-3 and -7 activity. Immunohistochemistry studies of the LH and FSH treated follicles indicated that cleaved caspase-3 was predominantly localized to the peripheral theca-interstitial cells (TIC). Western blot analysis and caspase-3 and -7 activity assays of the separated follicular compartments confirmed that both LH and FSH treatments significantly enhance caspase-3 and -7 activity in TIC. The elevation in caspase-3 and -7 activity in TIC was accompanied by an increase in apoptosis. Interestingly, LH and FSH also induced an increase in caspase-3 and -7 activity in GC, however this increase was accompanied by a decrease in apoptosis. Finally, we demonstrate that in freshly isolated preovulatory follicles and in antral follicles in intact ovaries, the expression level of pro-caspase-3 is significantly higher in TIC than in GC. Thus, LH and FSH have a dual effect on the cultured rat preovulatory follicle: an anti-apoptotic effect on GC and a pro-apoptotic effect on TIC.