Apoptosis in steroidogenic cells: structure-function analysis

Abstract

Granulosa cells are the main producers of the female sex steroid hormones, progesterone and estradiol, which are responsible for the cyclicity in ovarian function. Programmed cell death in the ovary plays a crucial role in limiting the number of follicles that can ovulate and thus prevents the development of more embryos than can successfully complete pregnancy. Granulosa cell apoptosis is regulated by the concerted action of endocrine, paracrine, and autocrine factors. These factors lead to the developmental decision of whether the steroidogenic cell will luteinize and enter the pathway leading to programmed cell death, or whether the life span of the luteinized cell will be prolonged to continue secretion of progesterone, which is essential for the maintenance of pregnancy. At the level of the individual cell, we find that enhanced steroidogenesis can be maintained during the initial steps of apoptosis as long as the steroidogenic apparatus remains intact. This can be achieved by a unique mechanism of compartmentalization of steroidogenic organelles in the perinuclear region and migration of the multicatalytic proteinase, the proteasome, to the apoptotic blebs. Reorganization of the actin cytoskeleton during apoptosis may provide an efficient barrier between the proteolytic activity and the steroidogenic activity in the apoptotic cell. It is suggested that steroidogenesis can be maintained in the apoptotic cells as long as the steroidogenic organelles bearing the steroidogenic apparatus remain intact.