Relevance of Steroid Biosynthesis, Metabolism and Transport in Pathophysiology and Drug Discovery

Steroid hormones have important roles in human physiology, but they are also implicated in the development of hormone-dependent cancers and various non-maligant diseases. Furthermore, changes in the concentrations of steroid hormones have important effects on the homeostasis of pre- and post-menopausal women, as well as of men in andropause. The associations of steroid hormones with pathophysiological processes and the altered mechanisms of their actions in disease are still not completely understood. It has been known for more than thirty years that in addition to their endocrine activity, steroid hormones act in an intracrine manner. In target organs, active androgens and estrogens can be formed from inactive, or less active, precursor steroid hormones, mainly dehydroepiandrosterone-sulfate (DHEA-S), and estrone-sulfate (E1-S) after their translocation into cells through the transporter proteins of the organic anion-transporting polypeptide (OATP) and organic anion-transporter (OAT) families. The combination of altered uptake of precursors, changed activation and action of estrogens and androgens, in concert with the changes in the metabolism and excretion may thus have major roles in the development of hormone-dependent malignant and non-malignant diseases. To date, the salient roles of the individual players in disease pathophysiology have not been precisely defined.

The aim of this Research Topic is to highlight the progress made in the field of steroid transport and intracrine actions and metabolism, with special emphasis on the involvement of these processes in the pathophysiology of hormone-dependent disorders and on the identification of novel drug targets.