Endocrine Abstracts (2016) 42 IL9 | DOI: 10.1530/endoabs.42.IL9

Regulating androgen action by steroid synthesis and metabolism

Matti Poutanen

Department of Physiology, Institute of Biomedicine, University of Turku, Finland.

Recent results from us and others have shown that concentrations of sex steroids in serum/circulation do not always reflect their intra-tissue levels in hormone-dependent tissues. This proposes that sex steroid metabolism plays a key role in determining the final concentration of active sex steroids in their target tissues. According to the current knowledge, members of three enzyme families, namely cytochrome P450 (CYP), aldo-keto reductase (AKR) and short-chain dehydrogenases/reductase (SDR) enzymes, have a key role in target tissue steroid metabolism. These enzymes potentially regulate the availability of highly potent ligands for the sex steroid receptors, including androgen receptor. A central part of our present studies is connected to our ability to generate novel pre-clinical in vivo models, the use of well-defined clinical cohorts, and the analysis of sex steroid concentrations with high sensitivity mass spectrometric methods (GC-MS/MS, LC-MS/MS) recently developed/under development by us. Accordingly, we have recently shown differential expression of HSD17B and other steroid synthetic enzymes and consequently different metabolism of estrogens and androgens in the eutopic and ectopic endometrium that partially could explain the hormone-dependent growth of endometriosis. Moreover, data from clinical tissue specimens as well as from our preclinical xenograft model of castration resistant prostate cancer indicate that active androgens are synthesized locally in the cancer tissue, and that the intra tissue DHT production is associated with altered expression of CYP, AKR SDR enzymes.

DOI: 10.1530/endoabs.42.IL9

Biographical details: Matti Poutanen, PhD, is Professor Physiology and Director of the Turku Center for Disease Modeling (www.tcdm.fi), Institute of Biomedicine, University of Turku, Finland. Research areas of interest: Biosynthesis and metabolism of steroids and lipids; Disorders in reproductive tissues and hormonal cancer. He has, 182 peer-reviewed publications with a total number of citations 5099.

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