ESPE Abstracts (2019) 92 S7.3

Widening the Horizon - Clinical Relevance of Steroid Hormone Pathways

Stefan A. Wudy

University of Giessen, Germany

While it had been widely believed at the end of last century that most problems in steroid metabolism had already been solved, and not much more significant discoveries were to be expected anymore, recent exciting observations and rediscoveries have initiated a renaissance in steroid metabolism research. These revolutionary findings have often been initially made in animals and have also significantly been driven by new steroid analytical techniques based on mass spectrometry. Thus, the classical (canonical) concepts of human steroid metabolism have become shattered and new insights into physiology and pathology of steroid related disorders have been provided, which will open up new avenues in diagnosis and therapy of these entities. For instance, observations in the Tammar wallaby led to the discovery of a novel androgenic synthetic route leading to dihydrotestosterone. This so called "back door or alternative pathway" bypasses the classical routes via DHEA, 4-androstenedione and testosterone. Furthermore, a new class of steroids, 11-oxygenated androgens, such as 11-keto-testosterone, has for long been known in teleost (bony) fish presenting important androgens. But it has only been until recently, that we have begun to understand their new and important role in the human being, particularly in hyperandrogenic conditions such as premature adrenarche, CAH or PCOS. New insights have also been achieved regarding complex, conjugated steroids, particularly the group of steroid sulfates. The identification of the cell membrane bound Sodium-dependent Organic Anion Transporter SOAT, an uptake carrier specifically transporting sulfated steroids, permitted recognition of an intracrine regulatory mechanism via the sulfatase pathway. This mechanism is restricted to cells that express an uptake carrier and STS together with steroid receptors and has been studied in human breast cancer and reproductive processes. A further, exciting novel finding is first in-vivo evidence for the adrenal gland as a drug metabolizer. While it has been hitherto believed that drug metabolism in mammals is limited to the liver and its cytochromes P450, it could now be shown that there is no strict subdivision between P450s involved in exogenous and endogenous metabolism. This talk will summarize the most relevant recent discoveries in the field of steroid metabolism and will illustrate their clinical significance and potential by work from others and our own group.

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