Steroid regulation during apoptosis of ovarian follicular cells.

ABRAHAM AMSTERDAM; ADA DANTES; KUMICO HOSOKAWA; CAROLINA SCHERE LEVY; FUMIKAZU KOTSUJI; DORIT AHARONI

STEROIDS

ELSEVIER SCIENCE INC

Año: 1998 vol. 63 p. 314 - 318

0039-128X

In each estrous cycle, only one follicle, the dominant follicle, reaches fullmaturation while the other recruited follicles become atretic in a processcharacteristic of programmed cell death. Moreover, the old corpus luteum formedin a previous cycle undergoes luteolysis by a mechanism also characteristic ofprogrammed cell death. Granulosa cells comprise the largest cell population ofthe ovarian follicle and are the main source of estradiol and progesterone in theovary. Their cyclic nature of differentiation and death determines the cyclicsecretion of female sex hormones and therefore serve as an excellent model forsteroid regulation during apoptosis. The characteristics of granulosa cellapoptosis, as in other cell types, are cell membrane blebbing, DNA degradationand protease activation. In addition, there are specific characteristics ofsteroidogenic granulosa cell apoptosis, as follows: 1) The trigger for apoptosis may be exerted by different effectors and signal transduction mechanisms duringfollicle development. For example, tumor necrosis factor (TNF) may triggergranulosa cell apoptosis at early stage of follicular development, while cAMP/p53signals may trigger this process only in mature preovulatory granulosa cells. 2) cross-talk between paracrine and endocrine signals, and between death genes andtumor suppressor genes, may determine the fate of the granulosa cell. 3) in themature follicle the follicular basement membrane plays an important role intransmitting survival signals and in prevention of apoptosis. 4) during theinitial steps of apoptosis, steroidogenesis may be increased due to clustering ofthe steroidogenic organelles in the perinuclear region and their exclusion fromthe apoptotic blebs. 5) Actin cytoskeleton reorganization plays an important rolein this compartmentalization as well as in transmitting survival signals exerted by basement membrane, laminin and growth factors which activate tyrosine kinasereceptors.