The majority of ovarian follicles undergo atresia, a hormonally contro
lled apoptotic process. Monitoring apoptotic DNA fragmentation provide
s a quantitative and sensitive endpoint to study the hormonal regulati
on of atresia in ovarian follicles. During follicle development, gonad
otropins, together with local ovarian growth factors (IGF-I, EGF/TGF-a
lpha, basic FGF) and cytokine (interleukin-1 beta), as well as estroge
ns, activate different intracellular pathways to rescue follicles from
apoptotic demise. In contrast, TNF-alpha, Fas ligand, presumably acti
ng through receptors with a death domain, and androgens are atretogeni
c factors. These diverse hormonal signals probably converge on selecti
ve intracellular pathways (including genes of the bcl-2 and ICE famili
es) to regulate apoptosis. With a constant loss of follicles from the
original stockpile, the ovary provides a unique model for studying the
hormonal regulation of apoptosis.