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Molecules (Basel, Switzerland) Jan 2023Steroid hormone molecules may exhibit very different functionalities based on the associated functional groups and their 3D arrangements in space, i.e., absolute...
Steroid hormone molecules may exhibit very different functionalities based on the associated functional groups and their 3D arrangements in space, i.e., absolute configurations and conformations. Infrared (IR) and vibrational circular dichroism (VCD) spectra of four different steroid hormones, namely dehydroepiandrosterone (DHEA), 17-methyltestosterone (MTTT), (16α,17)-epoxyprogesterone (Epoxy-P4), and dehydroepiandrosterone acetate (AcO-DHEA), were measured in deuterated dimethyl sulfoxide and some also in carbon tetrachloride. Extensive conformational searches were carried out using the recent developed conformer-rotamer ensemble sampling tool (CREST) which also accounts for solvent effects using an implicit solvation model. All the CREST conformational candidates were then reoptimized at the B3LYP-D3BJ/def2-TZVPD with the PCM of solvent. The good agreements between the experimental IR and VCD spectra and the theoretical simulations provide a conclusive information about their conformational distribution and absolute configurations. The experimental and theoretical IR and VCD spectra of AcO-DHEA in the carbonyl and alkene stretching region showed some discrepancies, and the possible causes related to solvent effects, large amplitude motions and levels of theory used in the modelling were explored in detail. As part of the investigation, additional calculations at the B3LYP-D3BJ/6-31++G (2d,p) and B3LYP-D3BJ/cc-pVTZ levels, as well as some 'mixed' calculations with the double-hybrid functional B2PLYP-D3 were also carried out. The results indicate that the double-hybrid functional is important for predicting the correct IR band pattern in the carbonyl and alkene stretching region.
PubMed: 36677830
DOI: 10.3390/molecules28020771 -
Genes May 2024It is widely known that all-female fish production holds economic value for aquaculture. , a preeminent economic species, exhibits a sex dimorphism, with females...
It is widely known that all-female fish production holds economic value for aquaculture. , a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales of for subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth of , while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes ( and ) while up-regulating male-related genes () in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role in sex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT in and offers an initial insight into the underlying mechanism of sexual reversal in this species.
Topics: Animals; Methyltestosterone; Male; Female; Sex Differentiation; Perciformes; Testis; Fishes; Fish Proteins
PubMed: 38790234
DOI: 10.3390/genes15050605 -
Integrative and Comparative Biology Nov 2012In the environment, there are aquatic pollutants that disrupt androgen signaling in fish. Laboratory and field-based experiments have utilized omics technologies to... (Review)
Review
In the environment, there are aquatic pollutants that disrupt androgen signaling in fish. Laboratory and field-based experiments have utilized omics technologies to characterize the molecular mechanisms underlying androgen-receptor agonism/antagonism. Transcriptomics and proteomics studies with 17β-trenbolone, a growth-promoting pharmaceutical found in water systems surrounding cattle feed lots, and androgens such as 17α-methyltestosterone and 17α-methyldihydrotestosterone, have been conducted in ovary and liver of fish that include the fathead minnow (FHM) (Pimephales promelas), common carp (Cyprinus carpio), Qurt medaka (Oryzias latipes), and zebrafish (Danio rerio). In this mini-review, we survey recent omics studies in fish and reveal that, despite the diversity of species and tissues examined, there are common cellular responses that are observed with waterborne androgenic treatments. Recurring themes in gene ontology include apoptosis, transport and oxidation of lipids, synthesis and transport of hormones, immune response, protein metabolism, and cell proliferation. However, we also discuss other mechanisms other than androgen receptor (AR) activation, such as responses to toxicant stress, estrogen receptor agonism, aromatization of androgens into estrogens, and inhibitory feedback mechanisms by high levels of androgens that may also explain molecular responses in fish. To further explore androgen-responsive protein networks, a sub-network enrichment analysis was performed on protein data collected from the livers of female FHMs exposed to 17β-trenbolone. We construct a putative AR-regulated protein/cell process network in the liver that includes B-lymphocyte differentiation, xenobiotic clearance, low-density lipoprotein oxidation, proliferation of smooth muscle cells, and permeability of blood vessels. We demonstrate that construction of protein networks can offer insight into cell processes that are potentially regulated by androgens.
Topics: Androgens; Animal Fins; Animals; Ecotoxicology; Environmental Monitoring; Fish Proteins; Fishes; Gene Expression Profiling; Liver; Proteomics; Receptors, Androgen; Sexual Development; Signal Transduction; Water Pollutants, Chemical
PubMed: 22596056
DOI: 10.1093/icb/ics072 -
Clinical Journal of the American... Apr 2019Many aspects of CKD management rely heavily on patient self-care, including medication and dietary adherence, self-monitoring of BP, and daily physical activity. Growing...
BACKGROUND AND OBJECTIVES
Many aspects of CKD management rely heavily on patient self-care, including medication and dietary adherence, self-monitoring of BP, and daily physical activity. Growing evidence suggests that incorporating smartphone-based applications can support self-care in CKD and chronic disease more generally.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We identified applications targeting patients with CKD by conducting a search of the US Apple App Store (iOS) and Google Play Store (Android) using the following four phrases: "kidney disease," "renal," "dialysis," and "kidney transplant." We considered the first 50 applications for each search term on each application store. We adapted a previously described framework for assessment of mobile health applications to account for kidney disease-specific content areas and evaluated applications on their types of patient engagement, quality, usability, and safety. Engagement and quality were assessed by both a patient and a nephrologist, usability was assessed by a patient, and safety was assessed by a nephrologist. Overall, two patients with CKD and three nephrologists performed the evaluations. We examined pairwise correlations between patient, nephrologist, and consumer ratings of application quality.
RESULTS
Our search strategy identified 174 unique applications on Android and 165 unique applications on iOS. After excluding applications that were not related to kidney disease, were not patient facing, or were last updated before 2014, 12 Android-only applications, 11 iOS-only applications, and five dual-platform applications remained. Patient and nephrologist application quality ratings, assessed by the net promoter score, were not correlated (=0.36; =0.06). Consumer ratings on the application stores did not correlate with patient ratings of application quality (=0.34; =0.18).
CONCLUSIONS
Only a small subset of CKD applications was highly rated by both patients and nephrologists. Patients' impressions of application quality are not directly linked to consumer application ratings or nephrologist impressions.
Topics: Attitude of Health Personnel; Humans; Mobile Applications; Nephrology; Patient Participation; Renal Insufficiency, Chronic; Self Care; Smartphone
PubMed: 30898873
DOI: 10.2215/CJN.10370818 -
Molecules (Basel, Switzerland) Mar 2021Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected...
Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. Following the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone ("oral turinabol"), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including the synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights into the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations to the D-ring.
Topics: Anabolic Agents; Gas Chromatography-Mass Spectrometry; Healthy Volunteers; Humans; Methandrostenolone; Methyltestosterone; Middle Aged; Reference Standards; Tandem Mass Spectrometry
PubMed: 33802606
DOI: 10.3390/molecules26051354 -
The Journal of the College of General... Mar 1964
Topics: Aging; Arteriosclerosis; Diuretics; Ethinyl Estradiol; Folic Acid; Geriatrics; Hearing Disorders; Hearing Loss, Noise-Induced; Humans; Hypertension; Methyltestosterone; Presbycusis; Smoking; Vasodilator Agents; Vitamin B Complex
PubMed: 14129699
DOI: No ID Found -
Zebrafish Dec 2022Severely skewed sex ratios in zebrafish stocks can pose significant hurdles for line propagation and sperm cryopreservation. To overcome female-biased sex ratios in... (Review)
Review
Severely skewed sex ratios in zebrafish stocks can pose significant hurdles for line propagation and sperm cryopreservation. To overcome female-biased sex ratios in stocks derived from imported sperm samples, the Zebrafish International Resource Center has implemented routine supplementation of larval food with 17α-methyltestosterone to skew gonadal sex differentiation toward masculinization. Resulting stocks averaged 80% males.
Topics: Male; Female; Animals; Zebrafish; Methyltestosterone; Semen; Gonads; Sex Differentiation
PubMed: 36318811
DOI: 10.1089/zeb.2022.0029 -
Chemosphere Sep 2017The influence of salinity on toxicity outcomes has been demonstrated for various contaminants, but has received limited attention for endocrine disrupting chemicals... (Review)
Review
The influence of salinity on toxicity outcomes has been demonstrated for various contaminants, but has received limited attention for endocrine disrupting chemicals (EDCs). Short-term laboratory tests using small-bodied fish are an important tool for evaluating impacts of EDCs on reproduction. Tests have been developed for both freshwater and estuarine/marine species, providing an opportunity to assess whether concentrations at which small-bodied fish respond to EDCs may be influenced by salinity. We conducted a semi-quantitative review of short-term laboratory tests with small-bodied fish exposed to EDCs, including 59 studies under freshwater conditions (7 species) and 23 studies conducted under saline conditions (5 species). We focused on two model estrogens [17α-ethinylestradiol and 17β-estradiol (E2)], and three androgens (17β-trenbolone, 5α-dihydrotestosterone and 17α-methyltestosterone). The lowest observed adverse effect concentration (LOAEC) for key reproductive endpoints was recorded, including sex-steroid and vitellogenin (VTG) levels, fecundity and fertilization. In 65.2% of cases, responses occurred at lower doses under freshwater compared to saline conditions, compared to only 4.3% of cases where fish responded to lower doses under saline conditions. The potential influence of salinity was more pronounced when estrogenic compounds were considered separately, with fish responding to lower doses under fresh compared to saline conditions in 90.5% of cases. Fecundity and E2 level were identified as the most sensitive endpoints for evaluating EDCs regardless of salinity. Interestingly, female VTG levels were a sensitive endpoint under freshwater but not saline conditions. Overall, our results suggest that salinity may be an important factor influencing how small-bodied fish respond to environmental EDCs.
Topics: Animals; Endocrine Disruptors; Estradiol; Female; Fishes; Fresh Water; Male; Reproduction; Salinity; Seawater; Vitellogenins; Water Pollutants, Chemical
PubMed: 28549324
DOI: 10.1016/j.chemosphere.2017.05.063 -
Journal of Managed Care Pharmacy : JMCP 2003Prescription Drugs Marketed in the United States Should Be Approved by the FDA. Two events in the drug regulatory approval process in recent years warrant the attention...
Prescription Drugs Marketed in the United States Should Be Approved by the FDA. Two events in the drug regulatory approval process in recent years warrant the attention of managed care pharmacists and should prompt reassessment of assumptions regarding drugs marketed in the United States. The first event, involving levothyroxine, received considerable public attention from 1999 through 2002. The second event involves an appellate court decision in May 1999 regarding combination product esterified estrogen and methyltestosterone (Estratest and Estratest HS, Solvay Pharmaceuticals). The circumstances of these events are noteworthy, and the social and market effects of each are sizable.
Topics: Drug Approval; Drug Industry; Humans; Jurisprudence; Legislation, Drug; Marketing; United States; United States Food and Drug Administration
PubMed: 14613456
DOI: 10.18553/jmcp.2003.9.4.366 -
Frontiers in Genetics 2022Assisted propagation of the European eel will lead to a closed production cycle supplying the aquaculture industry with juvenile glass eels. Females require long-term...
Assisted propagation of the European eel will lead to a closed production cycle supplying the aquaculture industry with juvenile glass eels. Females require long-term weekly treatment with pituitary extract (PE), which is stressful and causes abnormalities in oogenesis. We tested the effects of 17α-methyltestosterone (17 MT), as potent androgen activating the androgen receptor, and 17β-estradiol (E2), as an inducer of vitellogenesis, to shorten the duration of PE treatment.Four groups of feminized eels were subjected to a simulated migration and subsequent injection with implants containing 17 MT (17 MT-group), E2 (E2-group) or 17 MT plus E2 (17 MT + E2-group) to test for synergistic effects, or without any steroids as controls (C-group). The effects of a 2-months treatment were investigated by determining the eye index (EI), hepatosomatic and gonadosomatic index (HSI and GSI, respectively), plasma steroid concentrations by liquid chromatography mass spectrometry (LCMS), gonadal histology, expression of androgen receptors a and b (, ); estrogen receptor 1 (); FSH receptor (); vitellogenin receptor () and aromatase (), and the required number of weekly PE injections to fully mature. For many parameters, both the 17 MT and E2 groups showed an increase vs. controls, with the 17 MT + E2 group showing a synergistic effect, as seen for EI, GSI (3.4 for 17 MT and for E2, 6.6 for 17 MT + E2), oocyte diameter and , and expression. Concentrations of almost all focal steroids decreased with simulated migration and steroid treatment. Only eels of the 17 MT-group showed increased expression of and of , while expression increased 44-fold in the 17 MT + E2 group, highlighting that co-implantation is most effective in raising mRNA levels. Specific for eels of the E2 groups were vitellogenesis-associated changes such as an increase of HSI, plasma E2, and presence of yolk in the oocytes. Steroid treatments reduced the duration of PE treatment, again synergistically for co-implantation. In conclusion, E2 is necessary to start vitellogenesis, but 17 MT has specific effects on and expression. The combination is necessary for synergistic effects and as such, steroid implants could be applied in assisted reproduction protocols for European eel to improve oocyte quality leading to the production of more vital larvae.
PubMed: 36061169
DOI: 10.3389/fgene.2022.969202