Reduction of glucocorticoid receptor ligand binding by the 11-β hydroxysteroid dehydrogenase type 2 inhibitor, Thiram

Garbrecht, Mark R.; Krozowski, Zygmunt; Snyder, Jeanne M.; Schmidt, Thomas J.

doi:10.1016/j.steroids.2006.06.001

Cited by 21 publications

(16 citation statements)

References 41 publications

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“…Likewise, dithiocarbamates present in cosmetics and agricultural products inhibit 11β-HSD2 [191]. The dithiocarbamate pesticide thiram is also suspected to interfere with GR ligand binding [192]. In addition, other studies report inhibition of 11β-HSD2 by the organotins DBT [193] or TBT [194] by targeting critical cysteine residues necessary for enzymatic activity.…”

Section: Obesogens and Programming Of Metabolic Set Pointsmentioning

confidence: 99%

Endocrine disrupters as obesogens

Grün

Blumberg

2009

Molecular and Cellular Endocrinology

488

324

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The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity.

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Section: Obesogens and Programming Of Metabolic Set Pointsmentioning

confidence: 99%

Endocrine disrupters as obesogens

Grün

Blumberg

2009

Molecular and Cellular Endocrinology

488

324

View full text Add to dashboard Cite

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“…The phenylsulfamide fungicide tolylfluanid was shown to mimic the murine glucocorticoid corticosterone by inducing receptor nuclear translocation, binding to glucocorticoid response elements, and altering expression of glucocorticoid-responsive genes [86]. In addition to tolylfluanid, other compounds that have been shown to mimic or modulate glucocorticoid action at the glucocorticoid receptor include the dithiocarbamate fungicide thiram [87]; methylsulfonyl-PCBs [88,89]; dicyclohexylphthalate and endrin [46]; as well as BPA [46,90]. Thiram [91] as well as cadmium and tributyltin [92] have been shown to modulate the activity of 11β-HSD-2, while BPA has been shown to increase levels of 11β-HSD-1 [93].…”

Section: Pathways Of Metabolic Disruptionmentioning

confidence: 99%

The Hijacking of Cellular Signaling and the Diabetes Epidemic: Mechanisms of Environmental Disruption of Insulin Action and Glucose Homeostasis

Sargis

2014

Diabetes Metab J

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The burgeoning epidemic of metabolic disease causes significant societal and individual morbidity and threatens the stability of health care systems around the globe. Efforts to understand the factors that contribute to metabolic derangements are critical for reversing these troubling trends. While excess caloric consumption and physical inactivity superimposed on a susceptible genetic background are central drivers of this crisis, these factors alone fail to fully account for the magnitude and rapidity with which metabolic diseases have increased in prevalence worldwide. Recent epidemiological evidence implicates endocrine disrupting chemicals in the pathogenesis of metabolic diseases. These compounds represent a diverse array of chemicals to which humans are exposed via multiple routes in adulthood and during development. Furthermore, a growing ensemble of animal- and cell-based studies provides preclinical evidence supporting the hypothesis that environmental contaminants contribute to the development of metabolic diseases, including diabetes. Herein are reviewed studies linking specific endocrine disruptors to impairments in glucose homeostasis as well as tying these compounds to disturbances in insulin secretion and impairments in insulin signal transduction. While the data remains somewhat incomplete, the current body of evidence supports the hypothesis that our chemically polluted environment may play a contributing role in the current metabolic crisis.

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“…Indeed, decreases in HSD2 enzyme activity have been observed under conditions where HSD2 protein levels remain unchanged [14–16]. Therefore, we sought to explore the possibility that maternal low-protein diet induces changes in HSD2 enzyme activity in the absence of changes in actual HSD2 protein levels.…”

Section: Resultsmentioning

confidence: 99%

Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice

Garbrecht

Lamb

2013

ISRN Endocrinology

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The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation.

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Reduction of glucocorticoid receptor ligand binding by the 11-β hydroxysteroid dehydrogenase type 2 inhibitor, Thiram

Cited by 21 publications

References 41 publications

Endocrine disrupters as obesogens

Endocrine disrupters as obesogens

The Hijacking of Cellular Signaling and the Diabetes Epidemic: Mechanisms of Environmental Disruption of Insulin Action and Glucose Homeostasis

Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice

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