["Intracrinology". Autonomy and freedom of peripheral tissues]

Hormone-sensitive cancers, namely those of the prostate, breast and uterus, constitute one third of all cancers. In addition to the classical steroidogenic tissues, namely the ovaries, testes, adrenals and placenta, a large series of peripheral tissues possess all the enzymatic systems required for the formation of active androgens and estrogens from a relatively large supply of precursor steroids namely, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) provided by the adrenals. This report describes the structure, function and tissue-specific expression and regulation of the 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase, 17 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase gene families as well as some information about the aromatase gene. While, so far, most therapeutical approaches have been aimed and limited at controlling steroid formation by the classical steroidogenic tissues, it is clear that major efforts should now be turned towards intracrinology in order to better understand the physiological mechanisms controlling local steroid formation in peripheral target tissues and to develop improved therapy for hormono-sensitive diseases, especially breast, prostate, and uterine cancers.