Editorial
Integration of steroid research: Perspectives on environment factors, homeostasis in health, and disease treatment

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Aim and scope

Steroid molecules specifically control distinct aspects of cell proliferation, tissue differentiation, and normal physiological functions. Dysfunction in steroid signal transduction pathways leads to severe disorders and diminished life quality, and consequently pose an economic burden to society. Research in steroids so far has provided insights on their role in maintaining homeostasis and how to control or treat health issues such as human fertility, menopause or hypertension. However,

Topics

The topics of the Congress on Steroid Research included:

  • Environmental impact on human health

  • Steroids in disease (with the focus on diabetes, obesity and cancer)

  • Steroid receptor functionality

  • Mechanisms of signal transduction

  • Steroidogenesis and pre-receptor metabolism of steroids

  • Synthesis of modulators of signal transduction pathways and steroid metabolism

The chapters that follow will provide an overview of the speakers and oral contributions. More details can be found in the corresponding

Environmental challenge

The role of environmental exposures and their impact on epigenetics was introduced by T. Schug [K23]. Mechanisms of action include interference with epigenetic signaling (DNA methylation, chromatin remodeling or iRNA) and how some of these effects might be transmitted via the germ line for 3–4 generations. The concept of obesogens was evaluated by B. Blumberg [K22]. Tributylin (TBT, a persistant organic pollutant) acting via PPARγ promotes adipogenesis in vivo and TBT-exposure during early life

Diabetes and obesity

Epidemiologic observations indicate that females are less prone to metabolic syndrome and the development of insulin resistance than males. However, as presented by D.J. Clegg [K32] the onset of menopause leads to increased risk. Her studies on tissue-specific ERα-knock-out mice demonstrated the protective role of ERα. Females suffering from polycystic ovary syndrome PCOS have a high risk of type 2 diabetes (T2D) and cardiovascular disorders (CVD). A. Dunaif [K33] discovered susceptibility to

Cancer

Aromatase is the only P450 enzyme (CYP19) that converts androgens into estrogens and regulates the amount of estrogen that potentiates cellular proliferation. Aromatase inhibitors are used in the treatment of breast cancer. S. Chen [K26] described the molecular basis of de novo and acquired aromatase inhibitor resistance and presented cell lines specifically engineered for these studies. Similarly to breast cancer, a resistance to 17α-hydroxylase/17,20-lyase (CYP17) inhibitors e.g., abiraterone

Steroid receptors

In his plenary lecture J.Å. Gustafsson [K1] addressed the similarities and differences of ERα and ERβ structure and function which balance opposing proliferative and anti-proliferative activities, respectively. Present knowledge of gene regulatory networks influenced through ERβ including epithelial–mesenchymal transition (EMT) and cancer were presented. As depicted by G.L. Greene [K3] the pathways of estrogen receptors ERα and ERβ can be differentiated by subtype specific ligands (SERMs). Data

Signal transduction

Steroid hormones elicit rapid responses (s) via ion channels and kinases, and slow responses (hours to days) through nuclear-receptor mediated processes. These effects are referred to as the genomic and non-genomic effects, respectively. E.R. Prossnitz [K6] provided new data on the 7-transmembrane G protein-coupled receptor family (GRP30). The non-genomic role of GPR30 was demonstrated in the reproductive, nervous, immune and vascular systems, and in cancer and obesity. Thus GPR30 may represent

Steroidogenesis

The balance between activation and inactivation of steroid hormones drives the fate of cells and tissues. R.J. Auchus [K16] analysed the kinetics of conversions catalyzed by rat liver 3α-HSD (an AKR) and 17β-HSD1 (a SDR) and demonstrated that at equilibrium there was equal conversion of keto and hydroxyl-steroids, and that cofactor availability determines the net outcome of reactions. Peripheral steroidogenesis seems to be a major source of circulating steroids in postmenopausal women. As

Pre-receptor metabolism

An example of an enzyme mediating tissue specificity for steroid hormone action is the 11β-HSD1. As reviewed by A. Odermatt [K11] the enzyme is coupled to hexose-6-phosphate dehydrogenase (G6PDH) and converts cortisone to cortisol. In addition to glucocorticoids 11β-HSD1 was shown to metabolise the oxysterol 7-oxocholesterol to 7β-hydroxycholesterol as well as the secondary bile acid 7-oxolithocholic acid to chenodeoxycholic acid. P.M. Stewart [K12] reported on the role of 11β-HSD1 in

Chemistry of synthesis

Synthesis of modulators of steroid signal transduction pathways faces challenges involving specificity, similarity/differences to natural ligands and the difficulties involved in the synthesis of regio- and stereoisomers that characterizes natural product chemistry. D. Poirier [K18] reported on E2-based derivatives with C6-alkylamide and C16-bromoalkyl substituents and their further improvement with m-carbamoyl benzyl group at position 16β of E2. The later compound was an effective 17β-HSD type

Acknowledgements

We express our gratitude to Helmholtz Zentrum München, German Center for Environmental Health for the travel and logistics support. Funding for this conference was made possible in part by 1R13DK092108-01 grant from the National Institutes of Health. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial

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