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The Journal of Steroid Biochemistry and... Nov 2019Advances in technology have allowed for the sensitive, specific, and simultaneous quantitative profiling of steroid precursors, bioactive steroids and inactive... (Review)
Review
Advances in technology have allowed for the sensitive, specific, and simultaneous quantitative profiling of steroid precursors, bioactive steroids and inactive metabolites, facilitating comprehensive characterization of the serum and urine steroid metabolomes. The quantification of steroid panels is therefore gaining favor over quantification of single marker metabolites in the clinical and research laboratories. However, although the biochemical pathways for the biosynthesis and metabolism of steroid hormones are now well defined, a gulf still exists between this knowledge and its application to the measured steroid profiles. In this review, we present an overview of steroid hormone biosynthesis and metabolism by the liver and peripheral tissues, specifically highlighting the pathways linking and differentiating the serum and urine steroid metabolomes. A brief overview of the methodology used in steroid profiling is also provided.
Topics: Humans; Mass Spectrometry; Metabolome; Metabolomics; Steroids
PubMed: 31362062
DOI: 10.1016/j.jsbmb.2019.105439 -
Journal of Lipid Research Apr 2020Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and...
Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 μl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (-10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.
Topics: Analytic Sample Preparation Methods; Blood Chemical Analysis; Chromatography, Liquid; Female; Humans; Limit of Detection; Metabolomics; Pregnancy; Solvents; Steroids; Tandem Mass Spectrometry
PubMed: 31964762
DOI: 10.1194/jlr.D119000591 -
Steroids Jan 2020Steroids are an important biomolecule class for analysis due to their promise as biomarkers for various diseases and their abuse as performance enhancers in sports.... (Review)
Review
Steroids are an important biomolecule class for analysis due to their promise as biomarkers for various diseases and their abuse as performance enhancers in sports. Current analytical methods, including chromatography and nuclear magnetic resonance spectroscopy, fall short of being able to confidently analyze steroids, partly due to the large number of steroid isomers. Ion mobility spectrometry (IMS), a gas-phase ion separator, has shown potential for steroid analysis both in conjunction with liquid chromatography (LC) and as a stand-alone technique. This review will examine the current literature on IMS analysis of steroids. Analysis by LC-IMS will include examination of steroids and steroid glucuronides in human urine and serum samples for enhanced signal-to-noise ratios and higher confidence of identification. The stand-alone IMS analysis will examine the use of derivatization of steroids and formation of multimers to enhance resolution for steroid isomers analysis, where both methods have been shown to greatly increase the separation of steroid isomer species. However, these methods have not been applied to biological mixtures to assess their applicability to medical and forensic applications, which should be a future direction of this field.
Topics: Humans; Ion Mobility Spectrometry; Steroids
PubMed: 31672629
DOI: 10.1016/j.steroids.2019.108531 -
British Dental Journal Nov 2021
Topics: Steroids
PubMed: 34824411
DOI: 10.1038/s41415-021-3689-1 -
Methods in Enzymology 2023In mammals there are two 3-oxo-4-ene steroid reductases that generate either A/B-trans or A/B cis-ring junctions in the steroid nucleus known as steroid 5α- and 5β-...
In mammals there are two 3-oxo-4-ene steroid reductases that generate either A/B-trans or A/B cis-ring junctions in the steroid nucleus known as steroid 5α- and 5β- reductases, respectively. There is only one steroid 5β- reductase in each species and these are members of the aldo-keto-reductase (AKR) protein superfamily. The corresponding human enzyme is AKR1D1, and it plays an essential role in bile-acid biosynthesis. Germline mutations in AKR1D1 give rise to bile-acid deficiency. Because of its central role in steroid metabolism and need for detailed structure-function studies there is a need to purify the enzyme to homogeneity and in high yield. We report the purification of milligram amounts of crystallographic quality homogeneous recombinant protein for structure-function studies and its characterization.
Topics: Animals; Humans; Oxidoreductases; Steroids; Bile Acids and Salts; Mammals
PubMed: 37802574
DOI: 10.1016/bs.mie.2023.04.012 -
Best Practice & Research. Clinical... Jan 2021In this review, we provide a comprehensive overview of the utility of steroid profiling for diagnosis of management of overt Cushing syndrome and mild autonomous... (Review)
Review
In this review, we provide a comprehensive overview of the utility of steroid profiling for diagnosis of management of overt Cushing syndrome and mild autonomous cortisol secretion. A diagnosis of Cushing syndrome is made through a multistep process that includes confirmation of endogenous hypercortisolism, followed by determination of its cause. Steroid metabolomic testing applied to serum or urine steroids and their metabolites can provide additional and novel insights into alterations of steroid biosynthesis and metabolism and its causes. In particular, increased availability and advances in mass spectrometry-based steroid analysis, coupled with machine learning-based algorithms, have facilitated the development of tailored diagnostic and subtyping approaches for autonomous cortisol secretion and might be useful for detecting low grade autonomous glucocorticoid secretion and in predicting and monitoring of disease severity and associated comorbidities.
Topics: Algorithms; Cushing Syndrome; Diagnostic Techniques, Endocrine; Humans; Hydrocortisone; Metabolome; Severity of Illness Index; Steroids
PubMed: 33589355
DOI: 10.1016/j.beem.2021.101488 -
The Journal of Steroid Biochemistry and... Feb 2021For several decades now, the analysis of steroids has been a key tool in the diagnosis and monitoring of numerous endocrine pathologies. Thus, the available methods used... (Review)
Review
For several decades now, the analysis of steroids has been a key tool in the diagnosis and monitoring of numerous endocrine pathologies. Thus, the available methods used to analyze steroids in biological samples have dramatically evolved over time following the rapid pace of technology and scientific knowledge. This review aims to synthetize the advances in steroids' analysis, from classical approaches considering only a few steroids or a limited number of steroid ratios, up to the new steroid profiling strategies (steroidomics) monitoring large sets of steroids in biological matrices. In this context, the use of liquid chromatography coupled to mass spectrometry has emerged as the technique of choice for the simultaneous determination of a high number of steroids, including phase II metabolites, due to its sensitivity and robustness. However, the large dynamic range to be covered, the low natural abundance of some key steroids, the selectivity of the analytical methods, the extraction protocols, and the steroid ionization remain some of the current challenges in steroid analysis. This review provides an overview of the different analytical workflows available depending on the number of steroids under study. Special emphasis is given to sample treatment, acquisition strategy, data processing, steroid identification and quantification using LC-MS approaches. This work also outlines how the availability of steroid standards, the need for complementary analytical strategies and the improvement of calibration approaches are crucial for achieving complete steroidome quantification.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Endocrine System Diseases; Humans; Steroids; Tandem Mass Spectrometry
PubMed: 33259940
DOI: 10.1016/j.jsbmb.2020.105797 -
Journal of Medicinal Chemistry May 2023CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive... (Review)
Review
CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.
Topics: Male; Humans; Prostatic Neoplasms; Steroids; Steroid 17-alpha-Hydroxylase
PubMed: 37191389
DOI: 10.1021/acs.jmedchem.3c00442 -
The Journal of Steroid Biochemistry and... Jun 2019Adrenal steroidogenesis is a robust process, involving a series of enzymatic reactions that facilitate conversion of cholesterol into biologically active steroid... (Review)
Review
Adrenal steroidogenesis is a robust process, involving a series of enzymatic reactions that facilitate conversion of cholesterol into biologically active steroid hormones under the stimulation of angiotensin II, adrenocorticotropic hormone and other regulators. The biosynthesis of mineralocorticoids, glucocorticoids, and adrenal-derived androgens occur in separate adrenocortical zones as a result of the segregated expression of steroidogenic enzymes and cofactors. This mini review provides the principles of adrenal steroidogenesis, including the classic and under-appreciated 11-oxygenated androgen pathways. Several adrenal diseases result from dysregulated adrenal steroid synthesis. Herein, we review growing evidence that adrenal diseases exhibit characteristic modifications from normal adrenal steroid pathways that provide opportunities for the discovery of biomarker steroids that would improve diagnosis and monitoring of adrenal disorders.
Topics: Adrenal Gland Diseases; Adrenal Glands; Biomarkers; Biosynthetic Pathways; Humans; Steroids
PubMed: 30707926
DOI: 10.1016/j.jsbmb.2019.01.018 -
Ophthalmic Research 2012Steroids in susceptible individuals can cause a clinical condition similar to primary open-angle glaucoma. Five percent of the population are high steroid responders and... (Review)
Review
Steroids in susceptible individuals can cause a clinical condition similar to primary open-angle glaucoma. Five percent of the population are high steroid responders and develop an intraocular pressure (IOP) elevation of more than 15 mm Hg above baseline. IOP elevation may occur as early as 1 day to as late as 12 weeks after intravitreal triamcinolone in 20-65% of patients. On average, 75% of eyes with steroid implants require IOP-lowering therapy at some point within 3 years of follow-up. The exact mechanism of steroid-induced glaucoma is not totally understood, but decreased trabecular meshwork outflow is regarded as the main cause of IOP elevation. High-risk patients who receive steroids should be monitored closely and if they develop elevated IOP, steroids with lower potency or steroid-sparing agents should be used. The IOP usually returns to normal within 2-4 weeks after stopping the steroid. About 1-5% of patients do not respond to medical therapy and need surgery. Trabeculectomy, trabeculotomy, shunt surgery, and cyclodestructive procedures are among the methods employed. Removal of residual sub-Tenon or intravitreal steroids may help hasten the resolution of the steroid response. Early results with anecortave acetate, an analog of cortisol acetate with antiangiogenic activity, in controlling IOP have been promising.
Topics: Age Factors; Genetic Predisposition to Disease; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Risk Factors; Sex Factors; Steroids; Trabecular Meshwork
PubMed: 21757964
DOI: 10.1159/000328630