The intracrinology of breast cancer

The importance of intracrinology, or in situ production of steroids from circulating precursors, in breast cancer has been firmly established in estrogen actions on postmenopausal patients. Expression levels of various steroid synthesizing and/or metabolizing enzymes have been examined in human breast cancer tissues by a number of groups. The enzymes examined include those capable of converting circulating DHEA-S to sex steroids (STS and 3βHSDΔ4-5 isomerase), the group of enzymes that modulate the strength of both androgens and estrogens (17βHSD family) as well as the androgenic 5αR enzymes and the estrogenic aromatase enzyme. In addition to these DHEA-related metabolism pathways, other intracrine pathways involving progesterone and cholesterol have also been examined. Some risk factors of breast cancer development, including obesity, have also been postulated to interact with steroid metabolising pathways. In this review, we aimed to summarise the current state of knowledge regarding intracrine metabolism including expression levels of various enzymes and receptors, focusing particularly upon the importance of the production of biologically potent steroids from circulating sulfated precursors such as DHEA-S. In addition, we attempted to summarise the factors, both steroidal and non-steroidal, involved in the regulation of these enzymes and propose future directions for research in this particular field. The concept of intracrinology was first proposed over 20 years ago but there still remain many unanswered questions which could open new horizons for the understanding of intracrine metabolism in the breast. This article is part of a Special Issue entitled 'Essential role of DHEA'.