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The Journal of Steroid Biochemistry and... Jul 2015Many steroid hormones contain a Δ(4)-3-ketosteroid functionality that undergoes sequential reduction by 5α- or 5β- steroid reductases to produce 5α- or... (Review)
Review
Many steroid hormones contain a Δ(4)-3-ketosteroid functionality that undergoes sequential reduction by 5α- or 5β- steroid reductases to produce 5α- or 5β-dihydrosteroids; and a subsequent 3-keto-reduction to produce a series of isomeric tetrahydrosteroids. Apart from steroid 5α-reductase all the remaining enzymes involved in the two step reduction process in humans belong to the aldo-keto reductase (AKR) superfamily. The enzymes involved in 3-ketosteroid reduction are AKR1C1-AKR1C4. These enzymes are promiscuous and also catalyze 20-keto- and 17-keto-steroid reduction. Interest in these reactions exist since they regulate steroid hormone metabolism in the liver, and in steroid target tissues, they may regulate steroid hormone receptor occupancy. In addition many of the dihydrosteroids are not biologically inert. The same enzymes are also involved in the metabolism of synthetic steroids e.g., hormone replacement therapeutics, contraceptive agents and inhaled glucocorticoids, and may regulate drug efficacy at their cognate receptors. This article reviews these reactions and the structural basis for substrate diversity in AKR1C1-AKR1C4, ketosteroid reductases. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'.
Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Humans; Protein Binding; Steroids; Substrate Specificity
PubMed: 25500069
DOI: 10.1016/j.jsbmb.2014.12.003 -
Microbial Biotechnology Jul 2020Steroid hormones modulate development, reproduction and communication in eukaryotes. The widespread occurrence and persistence of steroid hormones have attracted public... (Review)
Review
Steroid hormones modulate development, reproduction and communication in eukaryotes. The widespread occurrence and persistence of steroid hormones have attracted public attention due to their endocrine-disrupting effects on both wildlife and human beings. Bacteria are responsible for mineralizing steroids from the biosphere. Aerobic degradation of steroid hormones relies on O as a co-substrate of oxygenases to activate and to cleave the recalcitrant steroidal core ring. To date, two oxygen-dependent degradation pathways - the 9,10-seco pathway for androgens and the 4,5-seco pathways for oestrogens - have been characterized. Under anaerobic conditions, denitrifying bacteria adopt the 2,3-seco pathway to degrade different steroid structures. Recent meta-omics revealed that microorganisms able to degrade steroids are highly diverse and ubiquitous in different ecosystems. This review also summarizes culture-independent approaches using the characteristic metabolites and catabolic genes to monitor steroid biodegradation in various ecosystems.
Topics: Biodegradation, Environmental; Ecosystem; Gonadal Steroid Hormones; Humans; Oxygenases; Steroids
PubMed: 31668018
DOI: 10.1111/1751-7915.13504 -
Physiological Research Dec 2021As gestational diabetes mellitus (GDM) is both a frequent and serious complication, steroid levels in pregnancy are extremely elevated and their role in pregnancy is... (Review)
Review
As gestational diabetes mellitus (GDM) is both a frequent and serious complication, steroid levels in pregnancy are extremely elevated and their role in pregnancy is crucial, this review focuses on the role of steroids and related substances in the GDM pathophysiology. Low SHBG levels are associated with insulin resistance and hyperinsulinemia, while also predicting a predisposition to GDM. Other relevant agents are placental hormones such as kisspeptin and CRH, playing also an important role beyond pregnancy, but which are synthesized here in smaller amounts in the hypothalamus. These hormones affect both the course of pregnancy as well as the synthesis of pregnancy steroids and may also be involved in the GDM pathophysiology. Steroids, whose biosynthesis is mainly provided by the fetal adrenal glands, placenta, maternal adrenal glands, and both maternal and fetal livers, are also synthesized in limited amounts directly in the pancreas and may influence the development of GDM. These substances involve the sulfated ?5 steroids primarily acting via modulating different ion channels and influencing the development of GDM in different directions, mostly diabetogenic progesterone and predominantly anti-diabetic estradiol acting both in genomic and non-genomic way, androgens associated with IR and hyperinsulinemia, neuroactive steroids affecting the pituitary functioning, and cortisol whose production is stimulated by CRH but which suppresses its pro-inflammatory effects. Due to the complex actions of steroids, studies assessing their predominant effect and studies assessing their predictive values for estimating predisposition to GDM are needed.
Topics: Diabetes, Gestational; Estradiol; Female; Humans; Placenta; Pregnancy; Progesterone; Steroids
PubMed: 35199547
DOI: 10.33549/physiolres.934794 -
Journal of Veterinary Diagnostic... May 2022Analysis of steroid and thyroid hormones is often performed in blood serum. Occasionally though, plasma samples are submitted in lieu of serum for exotic species such as...
Analysis of steroid and thyroid hormones is often performed in blood serum. Occasionally though, plasma samples are submitted in lieu of serum for exotic species such as tigers. However, blood tube anticoagulants may affect hormone values. We compared serum and heparin plasma results for 7 hormones in tigers. Serum and plasma samples were collected from 25 tigers and analyzed for progesterone, 17-hydroxyprogesterone, cortisol, androstenedione, testosterone, estradiol, and thyroxine. Using Lin concordance correlation, serum and heparin plasma measures agreed for all hormones except cortisol. However, Passing-Bablok regression only found agreement between serum and heparin plasma measures for androstenedione, testosterone, and estradiol. Median values between the 2 sample types were significantly ( < 0.05) different for progesterone, 17-hydroxyprogesterone, cortisol, and thyroxine. Our results suggest that, for the aforementioned hormones, serum and heparin plasma values may not always be comparable.
Topics: 17-alpha-Hydroxyprogesterone; Androstenedione; Animals; Estradiol; Heparin; Hydrocortisone; Progesterone; Serum; Steroids; Testosterone; Thyroid Hormones; Thyroxine; Tigers
PubMed: 35404190
DOI: 10.1177/10406387221090538 -
Frontiers in Immunology 2019Plasma exchange has been widely used in autoimmune neurological diseases and is the standard treatment for myasthenia gravis crisis and Guillain-Barre syndrome. A... (Review)
Review
Plasma exchange has been widely used in autoimmune neurological diseases and is the standard treatment for myasthenia gravis crisis and Guillain-Barre syndrome. A growing body of research suggests that, in the clinical application of steroid-responsive encephalopathy, such as for Hashimoto's encephalopathy, limbic encephalitis, systemic lupus erythematosus encephalopathy, ANCA-associated vasculitis encephalopathy, and acute disseminated encephalomyelitis, plasma exchange is a safe, and effective option when steroids or other immunosuppressive therapies are ineffective in the short term or when contraindications are present. Additionally, plasma exchange can also be used alone or in combination with steroids, immunoglobulins, or other immunosuppressive agents to treat steroid-responsive encephalopathy. This paper reviews the clinical application of plasma exchange in steroid-responsive encephalopathy, including its indications, onset time, course, curative effects, and side effects.
Topics: Brain Diseases; Humans; Plasma Exchange; Steroids
PubMed: 30873174
DOI: 10.3389/fimmu.2019.00324 -
The Journal of Neuroscience : the... Apr 2018Steroids play vital roles in animal physiology across species, and the production of specific steroids is associated with particular internal biological functions. The... (Review)
Review
Steroids play vital roles in animal physiology across species, and the production of specific steroids is associated with particular internal biological functions. The internal functions of steroids are, in most cases, quite clear. However, an important feature of many steroids (their chemical stability) allows these molecules to play secondary, external roles as chemical messengers after their excretion via urine, feces, or other shed substances. The presence of steroids in animal excretions has long been appreciated, but their capacity to serve as chemosignals has not received as much attention. In theory, the blend of steroids excreted by an animal contains a readout of its own biological state. Initial mechanistic evidence for external steroid chemosensation arose from studies of many species of fish. In sea lampreys and ray-finned fishes, bile salts were identified as potent olfactory cues and later found to serve as pheromones. Recently, we and others have discovered that neurons in amphibian and mammalian olfactory systems are also highly sensitive to excreted glucocorticoids, sex steroids, and bile acids, and some of these molecules have been confirmed as mammalian pheromones. Steroid chemosensation in olfactory systems, unlike steroid detection in most tissues, is performed by plasma membrane receptors, but the details remain largely unclear. In this review, we present a broad view of steroid detection by vertebrate olfactory systems, focusing on recent research in fishes, amphibians, and mammals. We review confirmed and hypothesized mechanisms of steroid chemosensation in each group and discuss potential impacts on vertebrate social communication.
Topics: Animal Communication; Animals; Chemoreceptor Cells; Humans; Nonverbal Communication; Pheromones, Human; Social Behavior; Steroids
PubMed: 29519850
DOI: 10.1523/JNEUROSCI.2488-17.2018 -
Indian Journal of Pharmacology 2020Although the use of steroids in the management of COVID-19 has been addressed by a few systematic review and meta-analysis, however, they also used data from "SARS-CoV"... (Meta-Analysis)
Meta-Analysis
PURPOSE
Although the use of steroids in the management of COVID-19 has been addressed by a few systematic review and meta-analysis, however, they also used data from "SARS-CoV" and "MERS-CoV." Again, most of these studies addressed only one severity category of patients or addressed only one efficacy endpoint (mortality). In this context, we conducted this meta-analysis to evaluate the efficacy and safety of steroid therapy among all severity categories of patients with COVID-19 (mild to moderate and severe to critical category) in terms of "mortality," "requirement of mechanical ventilation," "requirement of ICU" and clinical cure parameters.
METHODS
11 databases were screened. Only randomized controlled trials (RCTs) or high quality (on the basis of risk of bias analysis) comparative-observational studies were included in the analysis. RevMan5.3 was used for the meta-analysis.
RESULTS
A total of 15 studies (3 RCT and 12 comparative-observational studies) were included. In the mechanically-ventilated COVID-19 population, treatment with dexamethasone showed significant protection against mortality (single study). Among severe and critically ill combined population, steroid administration was significantly associated with lowered mortality (risk ratio [RR] 0.83 [0.76-0.910]), lowered requirement of mechanical ventilation (RR 0.59 [0.51-0.69]), decreased requirement of intensive care unit (ICU) (RR 0.62 [0.45-0.86]), lowered length of ICU stay (single-study) and decreased duration of mechanical ventilation (two-studies). In mild to moderate population, steroid treatment was associated with a higher "duration of hospital stay," while no difference was seen in other domains. In patients at risk of progression to "acute respiratory distress syndrome," steroid administration was associated with "reduced requirement of mechanical ventilation" (single-study).
CONCLUSION
This study guides the use of steroid across patients with different severity categories of COVID-19. Among mechanically ventilated patients, steroid therapy may be beneficial in terms of reduced mortality. Among "severe and critical" patients; steroid therapy was associated with lowered mortality, decreased requirement of mechanical ventilation, and ICU. However, no benefit was observed in "mild to moderate" population. To conclude, among properly selected patient populations (based-upon clinical severity and biomarker status), steroid administration may prove beneficial in patients with COVID-19.
Topics: Dexamethasone; Humans; Steroids; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33666200
DOI: 10.4103/ijp.ijp_1146_20 -
Ugeskrift For Laeger Aug 2014The risk of steroid-induced elevation of intraocular pressure and glaucoma is clinical relevant and require monitoring of patients at risk. The risk depends on route of... (Review)
Review
The risk of steroid-induced elevation of intraocular pressure and glaucoma is clinical relevant and require monitoring of patients at risk. The risk depends on route of administration, potency and individual risk factors such as primary open glaucoma (POAG), first-degree relative with POAG, age (children) and myopia. Steroid-induced elevation of intraocular pressure is most commonly associated with ocular application and systemic administration but may occur after periocular cutaneous application and nasal and inhalation therapy in patients with individual risk factors.
Topics: Glaucoma; Glucocorticoids; Humans; Intraocular Pressure; Ocular Hypertension; Risk Factors; Steroids
PubMed: 25293703
DOI: No ID Found -
Molecules (Basel, Switzerland) May 2022Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl... (Review)
Review
Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl estradiol, testolactone, progesterone, cortisone, cortisol, prednisone, and prednisolone. The world market for AD and ADD (androstadienedione) exceeds 1000 tons per year, which stimulates the pharmaceutical industry's search for newer and cheaper raw materials to produce steroidal compounds. In light of this interest, we aimed to investigate the progress of AD biosynthesis from phytosterols by prospecting scientific articles (Scopus, Web of Science, and Google Scholar databases) and patents (USPTO database). A wide variety of articles and patents involving AD and phytosterol were found in the last few decades, resulting in 108 relevant articles (from January 2000 to December 2021) and 23 patents of interest (from January 1976 to December 2021). The separation of these documents into macro, meso, and micro categories revealed that most studies (articles) are performed in China (54.8%) and in universities (76%), while patents are mostly granted to United States companies. It also highlights the fact that AD production studies are focused on "process improvement" techniques and on possible modifications of the "microorganism" involved in biosynthesis (64 and 62 documents, respectively). The most-reported "process improvement" technique is "chemical addition" (40%), which means that the addition of solvents, surfactants, cofactors, inducers, ionic liquids, etc., can significantly increase AD production. Microbial genetic modifications stand out in the "microorganism" category because this strategy improves AD yield considerably. These documents also revealed the main aspects of AD and ADD biosynthesis: sp. (basonym: sp.) (40%) and (known previously as ) (32%) are the most recurrent species studied. Microbial incubation temperatures can vary from 29 °C to 37 °C; incubation can last from 72 h to 14 days; the mixture is agitated at 140 to 220 rpm; vegetable oils, mainly soybean, can be used as the source of a mixture of phytosterols. In general, the results obtained in the present technological prospecting study are fundamental to mapping the possibilities of AD biosynthesis process optimization, as well as to identifying emerging technologies and methodologies in this scenario.
Topics: Androgens; Androstenedione; Biotransformation; Mycobacteriaceae; Phytosterols; Steroids
PubMed: 35630641
DOI: 10.3390/molecules27103164 -
European Review For Medical and... Jul 2023Acute spinal cord injury (SCI) is a devastating disease that causes immense physical and mental harm to the patient and the family, and society and requires a... (Review)
Review
Acute spinal cord injury (SCI) is a devastating disease that causes immense physical and mental harm to the patient and the family, and society and requires a multidisciplinary approach to treatment. The study of acute SCI has a long history but is still emerging. As the mechanism and pathophysiology of acute SCI are continuously being studied and explored, the treatment of SCI has developed significantly. Steroids are thought to provide neuroprotection in patients with acute SCI by improving perfusion, reducing edema, modulating inflammatory cells, and inhibiting lipid peroxidation, leading to their widespread application in clinical medicine. The use of steroids for SCI is controversial because of limited clinical evidence. With the accumulation of evidence on the effectiveness of steroid treatment in improving neurological function and the evidence of severe side effects, a gradual change in the treatment of SCI with steroids has become inevitable. Most scholars have focused on the routine use of steroids because of the indefinite improvement in neurological function and the occurrence of severe adverse events. Therefore, this review aims to provide an overview of the mechanism, progress, and related controversies to comprehensively understand the value and future direction of steroid application in acute SCI.
Topics: Humans; Spinal Cord Injuries; Steroids; Edema; Spinal Cord
PubMed: 37458661
DOI: 10.26355/eurrev_202307_32966