Hormone nuclear receptors and their ligands: role in programmed cell death (review).

Programmed cell death (PCD) represents a highly efficient and very sophisticated system for removing cells from the surrounding environment. As deadly as it may be, PCD is essential for elimination of aberrant cells and the survival of the living organism as a whole. Therefore, PCD is meticulously controlled, and among major regulatory actors belong small lipophilic hormones acting as ligands of the members of a nuclear receptor superfamily. In general, these hormones which include steroids, thyroids, retinoids, vitamin D3 derivatives, serve a critical role in the maintenance of homeostasis. For example, steroids regulate metabolism, reproduction, and development in animals that are as different as insects and humans. During animal development, steroids trigger distinct responses including cell differentiation and programmed cell death. Thus, hormones have been linked to numerous human health problems, and defects in hormone triggered programmed cell death may result e.g. in the survival of tumor cells or degenerative disorders. In vertebrate and invertebrate organisms where steroids including androgens, estrogens, progesterone, glucocorticoids and ecdysteroids regulate cell death, intensive study of this processes has resulted in a wealth of new information regarding how small lipophilic hormones contribute to cell demise within an organism. There is a great knowledge on the execution phase of apoptosis, the most frequent form of programmed cell death, and on the variety of its inducers. Even though we will review also recent advances on the topics various small ligands in the role of inducers, nevertheless we want to highlight the mechanisms that links action of hormones to the activation of apoptotic execution, the complex of processes, which are poorly understood so far.