Why do humans have two glucocorticoids: A question of intestinal fortitude

Morris, David J.

doi:10.1016/j.steroids.2015.06.017

Cited by 16 publications

(8 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…higher mineralocorticoid activity and lower susceptibility to 11β-hydroxysteroid dehydrogenase types 1 and 2) that might cause it and its 5α-metabolites to affect blood pressure significantly. 27…”

Section: Discussionmentioning

confidence: 99%

Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype

et al. 2016

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected for further study 7 polymorphisms located up to 2 kilobases upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified three of these (rs138009835, rs2150927 and rs2486758) as having significant functional effects. We then analysed association between the 7 polymorphisms and urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we employed as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only one of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure-associated polymorphisms identified in previous studies. In conclusion, we have identified, characterised and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835 – which we associate with changes in aldosterone level – is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype

et al. 2016

View full text Add to dashboard Cite

show abstract

“…116 (2015) No. 4, p. 268-278 under certain physiological conditions corticosterone has additional biochemical functions over and above those of cortisol (Morris, 2015). Stress is a common reaction to having blood drawn, brought on either directly by the insertion of the needle or even more so by the fear that precedes it.…”

Section: )mentioning

confidence: 99%

Changes in the Concentrations of Corticoid Metabolites – The Effect of Stress, Diet and Analytical Method

et al. 2015

View full text Add to dashboard Cite

A precisely measured corticoid level is important for decision-making in daily clinical practice. These levels can be influenced in the pre-analytical phase, when the effect of stress, timing, and diet can be important. The aim of this study was to elucidate optimal conditions for blood sampling as well as the choice of analytical methods, which they will be used in measuring of corticoids. By studying ten women, we focused on the influences of the stress of cannulation and a large lunchtime meal on cortisol, cortisone, aldosterone and corticosterone levels. We further compared results of cortisol measurements from RIA and LC-MS/MS. Stress from cannulation caused increase of cortisol, cortisone and corticosterone already, when the cannula was being inserted. This indicates that this increase is stimulated by fear of the blood withdrawing rather, than just by the needle insertion itself. The effect of stress on corticosterone disappeared after an hour, while effect on other corticoids was still apparent. Concerning the lunchtime meal, we found an increase in all measured corticoids between 11 and 12 o'clock. After the food, there were marked decreases in cortisone and aldosterone, while declining levels of cortisol and corticosterone had rather plateaus. We compared cortisol in 90 plasma samples measured by a commercial RIA kit and the LC-MS/MS method. Results from both methods showed a strong correlation (r=0.85). When measuring corticoid metabolites, the chosen analytical method, eliminating stress factors, and precisely timed blood sampling considering the daily rhythm and food intake are critical.

show abstract

“…Cortisol and corticosterone are the primary C21 glucocorticoids present in humans. However, cortisol concentrations are about 10 times greater than corticosterone [154]. Cortisol plays a major role in the stress response and maintenance of blood glucose concentration, as well as in inhibition of protein synthesis in muscle, of lipogenesis in fat cells, and of the immune system [155].…”

Section: Host Glucocorticoid Synthesismentioning

confidence: 99%

Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega

Doden

Ridlon

2021

Microorganisms

View full text Add to dashboard Cite

Bile acids (BAs) and glucocorticoids are steroid hormones derived from cholesterol that are important signaling molecules in humans and other vertebrates. Hydroxysteroid dehydrogenases (HSDHs) are encoded both by the host and by their resident gut microbiota, and they reversibly convert steroid hydroxyl groups to keto groups. Pairs of HSDHs can reversibly epimerize steroids from α-hydroxy conformations to β-hydroxy, or β-hydroxy to ω-hydroxy in the case of ω-muricholic acid. These reactions often result in products with drastically different physicochemical properties than their precursors, which can result in steroids being activators or inhibitors of host receptors, can affect solubility in fecal water, and can modulate toxicity. Microbial HSDHs modulate sterols associated with diseases such as colorectal cancer, liver cancer, prostate cancer, and polycystic ovary syndrome. Although the role of microbial HSDHs is not yet fully elucidated, they may have therapeutic potential as steroid pool modulators or druggable targets in the future. In this review, we explore metabolism of BAs and glucocorticoids with a focus on biotransformation by microbial HSDHs.

show abstract

Why do humans have two glucocorticoids: A question of intestinal fortitude

Cited by 16 publications

References 85 publications

Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype

Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype

Changes in the Concentrations of Corticoid Metabolites – The Effect of Stress, Diet and Analytical Method

Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega

Contact Info

Product

Resources

About