The 17beta-hydroxysteroid
dehydrogenases (17beta-HSDs) play an important role in the regulation of
steroid hormones, such as
estrogens and
androgens, by catalysing the reduction of
17-ketosteroids or the oxidation of 17beta-hydroxysteroids using
NAD(P)H or
NAD(P)(+) as cofactor. The
enzyme activities associated with the different 17beta-HSD
isoforms are widespread in human tissues, not only in classic steroidogenic tissues, such as the testis, ovary, and placenta, but also in a large series of peripheral intracrine tissues. In the nineties, several new types of 17beta-HSD were reported, indicating that a fine regulation is carried out. More importantly, each type of 17beta-HSD has a selective substrate affinity, directional (reductive or oxidative) activity in intact cells, and a particular tissue distribution. These findings are important for understanding the mode of action of the 17beta-HSD family. From a therapeutic point of view, this means that selectivity of
drug action could be achieved by targeting a particular 17beta-HSD
isozyme. Consequently, each study that leads to better knowledge of the inhibition of 17beta-HSDs deserves attention from scientists working in this and related fields. Being involved in the last step of the biosynthesis of sex
steroids from
cholesterol, the 17beta-HSD family constitutes an interesting target for controlling the concentration of
estrogens and
androgens. Thus, inhibitors of 17beta-HSDs are useful tools to elucidate the role of these
enzymes in particular
biological systems or for a therapeutic purpose, especially to block the formation of active
hydroxysteroids that stimulate estrogeno-sensitive pathologies (breast, ovarian, and
endometrium cancers) and androgeno-sensitive pathologies (
prostate cancer,
benign prostatic hyperplasia,
acne,
hirsutism, etc). Few review articles have however focussed on 17beta-HSD inhibitors although this family of steroidogenic
enzymes includes interesting therapeutic targets for the control of several diseases. Furthermore, inhibitors of 17beta-HSDs constitute a growing field in biomedical research and there is a need for an exhaustive review on this topic. In addition to giving an up-to-date description of inhibitors of all 17beta-HSD
isoforms (types 1-8), the present review will also address, when possible, the
isoform selectivity and residual estrogenic or androgenic activity often associated with steroidal inhibitors.