Perspectives in understanding the role of human 17beta-hydroxysteroid dehydrogenases in health and disease.

Steroid signaling involves specific receptors that mediate genomic effects and many further proteins responsible for fast nongenomic activities. Metabolism at the position 17 of the steroid scaffold plays a pivotal role in the final regulation of the biological potency of steroid hormones. Enzymes responsible for that, the 17beta-hydroxysteroid dehydrogenases (17beta-HSD), act as carbonyl reductases and require cofactors for their catalytic activity. There is a substantial amount of evidence that human 17beta-HSDs are as well involved in the metabolic pathways of retinoids and fatty acid beyond that which has so far been anticipated. At present fourteen 17beta-HSDs have been annotated and characterized, and more might follow. Many of 17beta-HSDs have been shown to be involved in the pathogenesis of human disorders and are targets for therapeutic intervention. Strategies on deciphering the physiological role of the 17beta-HSD and the genetic predisposition for associated diseases will be presented involving analyses of animal models.