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Analytical Methods : Advancing Methods... Dec 2023Methyltestosterone is one of the banned drugs in aquaculture, and it should be monitored in food-producing animals. 17α-Methyl-5β-androstane-3α,17β-diol, as the main...
Methyltestosterone is one of the banned drugs in aquaculture, and it should be monitored in food-producing animals. 17α-Methyl-5β-androstane-3α,17β-diol, as the main metabolite of methyltestosterone in vertebrates, could be used as another marker for controlling the administration of methyltestosterone, due to its high residual concentration and slow elimination rate. In this study, an analytical method based on gas chromatography-mass spectrometry (GC-MS) was developed and validated for the simultaneous determination of methyltestosterone and its main metabolite in fish. After pretreatment by liquid-liquid extraction with -hexane and solid phase extraction with C and NH columns, the target analytes in the muscle tissues were extracted and concentrated, and the influence of the sample matrix was eliminated. Then, the prepared samples were separated and detected with GC-MS in the selected ion monitoring (SIM) mode. Methyltestosterone-D was chosen as the internal standard for quantitation. After optimization, the limits of detection for methyltestosterone and 17α-methyl-5β-androstane-3α,17β-diol were 20 μg kg and 15 μg kg, respectively. The limits of quantitation were both 50 μg kg. The calibration curves showed good linearity in the concentration range from 50.0 ng mL to 500.0 ng mL. The correlation coefficients of methyltestosterone and 17α-methyl-5β-androstane-3α,17β-diol were more than 0.9990. The recoveries of the analytes in real samples were in the range of 99.7-116.6% with the relative standard deviation of 5.2-8.3%. The established method could meet the demand for simultaneous detection of methyltestosterone and its major metabolite, and it could be used to provide more information on the abuse of methyltestosterone in food-producing animals.
Topics: Animals; Gas Chromatography-Mass Spectrometry; Methyltestosterone; Androstanes; Fishes; Calibration
PubMed: 38086623
DOI: 10.1039/d3ay01646c -
General and Comparative Endocrinology Jul 2022Estrogens and androgens that coexist in the aquatic environment could potentially affect shellfish, however, endocrine disrupting effects of them in shellfish are...
Estrogens and androgens that coexist in the aquatic environment could potentially affect shellfish, however, endocrine disrupting effects of them in shellfish are significant. As an important aquaculture shellfish in China, Hyriopsis cumingii has remarkable economic benefits. In this study, the effects of endocrine disrupting chemicals on the steroid synthase Hc-Cyp17a in the male and female gonads of the H. cumingii were assessed by exposing juvenile mussels to cultured waters containing 17β-Estradiol (E2) and 17α-Methyltestosterone (MT) for 28 days. At the same time, the E2 content in the four stages of gonadal development, the expression changes of Hc-Cyp17a in gonadal development and its localization in the mature gonad were measured to explore the relationship between genes and hormones. The results showed that both E2 and MT at 50 ng/L and 200 ng/L could affect the transcription level of Hc-Cyp17a, which was inhibited initially and promoted in post-development. E2 content was positively correlated with gonadal development stage, which was in mussel. By tracing the expression of Hc-Cyp17a, difference was found during different developmental periods. The expression level in ovary was higher than that in testis during gonadal development of 1/ 2/ 3-year-old mussels and showed an increasing trend with age. Furthermore, the expression levels in 6 tissues of mature individuals were measured and it showed that there was a significant difference between male and female in the gonads (p < 0.01). In situ hybridization, it suggested that Hc-Cyp17a was significantly signaled in the follicular wall and oocyte of female and in the follicular membrane of testis, respectively. These results could play a vital role in assessing and understanding the effects of aquatic environment on the endocrine system of H. cumingii.
Topics: Animals; Endocrine Disruptors; Estradiol; Estrogens; Female; Gonadal Steroid Hormones; Gonads; Male; Methyltestosterone; Steroid 17-alpha-Hydroxylase
PubMed: 35314150
DOI: 10.1016/j.ygcen.2022.114028 -
Steroids Jan 2016Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry... (Review)
Review
Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry of the steroidal hormone 17α-methyltestosterone that is approved by Food and Drug Administration (FDA) in the United States as an androgen for estrogen-androgen hormone replacement therapy treatment. The analog also offers special possibilities for the prevention/treatment of hormone-sensitive cancers. The testosterone skeleton has important functionalities in the molecule that can act as a carbonyl component, an active methylene compound, α,β-unsaturated enone and tertiary hydroxyl group in various chemical reactions to access stereoisomeric steroidal compounds with potent activity. In addition, microbiological methods of synthesis and transformation of this hormone are presented.
Topics: Biotransformation; Hormones; Humans; Methyltestosterone
PubMed: 26639430
DOI: 10.1016/j.steroids.2015.11.004 -
Comparative Biochemistry and... Sep 2016Rare minnow (Gobiocypris rarus), a Chinese native species, are an excellent emerging model organism for aquatic toxicity testing and chemical safety assessment. "Big... (Review)
Review
Rare minnow (Gobiocypris rarus), a Chinese native species, are an excellent emerging model organism for aquatic toxicity testing and chemical safety assessment. "Big data" omics approaches (i.e., genomics, proteomics, and metabolomics) to inform mechanistic toxicology are now applied to studies in rare minnows to better understand toxicity and molecular pathways perturbed by chemicals. This review highlights recent applications of toxicogenomics to study changes in the gene and protein expression profiles in rare minnows in response to chemicals. Here we briefly describe studies that utilized cDNA microarrays in characterization of the cellular effects of rare minnows in single and mixed chemical exposures. Then we compare gel-based proteomics studies in liver of rare minnows following treatment with endocrine disrupting chemicals including 17β-estradiol, 17α-methyltestosterone, pentachlorophenol, and perfluorooctanoic acid. A total of 90 proteins identified in these studies were functionally annotated and categorized. These responsive proteins have roles in biological processes that include metabolism (37.8%), response to oxidation/chemicals (16.7%), signal transduction (11.1%), transport (10%), cytoskeleton (6.7%) and others (17.8%). In addition, recent investigations of endocrine disrupting effects and neurotoxicity of benzotriazole, an emerging contaminant, are summarized. The objective is to continue to enrich genome and protein databases for this species and to integrate molecular datasets to consider temporal effects and complex regulation at the level of the genome and proteome.
Topics: Animals; Cyprinidae; Endocrine Disruptors; Proteome; Toxicogenetics; Water Pollutants, Chemical
PubMed: 27373348
DOI: 10.1016/j.cbd.2016.06.007 -
Climacteric : the Journal of the... Dec 2014Androgens play a pivotal role in cardiovascular function and their effects differ between men and women. In postmenopausal women, testosterone replacement within... (Review)
Review
Androgens play a pivotal role in cardiovascular function and their effects differ between men and women. In postmenopausal women, testosterone replacement within physiological levels is associated with overall well-being. However, a definitive explanation as to how androgens have an impact on cardiovascular health in postmenopausal women and whether they may be used for cardiovascular treatment has yet to be established. With these aims, a systematic review of the existing studies on the link between androgens and cardiovascular disease and the effects of testosterone therapy on cardiovascular outcomes in postmenopausal women has been conducted. The few existing studies on cardiovascular outcomes in postmenopausal women indicate no effect or a deleterious effect of increasing androgens and increased cardiovascular risk. However, there is evidence of a favorable effect of androgens on surrogate cardiovascular markers in postmenopausal women, such as high density lipoprotein cholesterol, total cholesterol, body fat mass and triglycerides. Further studies are therefore needed to clarify the impact of therapy with androgens on cardiovascular health in postmenopausal women. The cardiovascular effect of testosterone or methyltestosterone with or without concomitant estrogens needs to be elucidated.
Topics: Androgens; Cardiovascular Diseases; Cardiovascular System; Estrogen Replacement Therapy; Female; Humans; MEDLINE; Methyltestosterone; Middle Aged; Postmenopause; Risk Factors; Testosterone
PubMed: 24559253
DOI: 10.3109/13697137.2014.887669 -
Expert Opinion on Emerging Drugs Sep 2016Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male... (Review)
Review
INTRODUCTION
Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable.
AREAS COVERED
The available literature of T and alternative treatments for male hypogonadism are discussed.
EXPERT OPINION
Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.
Topics: Administration, Cutaneous; Adolescent; Androgens; Animals; Gels; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Testosterone
PubMed: 27552127
DOI: 10.1080/14728214.2016.1226799 -
Comparative Biochemistry and... 2023Steroidogenesis is an important biological process for gonadal differentiation and development. In mammals, 3β-hydroxysteroid dehydrogenase 7 (HSD3B7) could convert...
Steroidogenesis is an important biological process for gonadal differentiation and development. In mammals, 3β-hydroxysteroid dehydrogenase 7 (HSD3B7) could convert 3β-hydroxy of 7α-hydroxycholesterol into a ketone and form 7α-hydroxy-4-cholesten-3-one, which may affect steroidogenesis. However, in fish, the study of Hsd3b7 is still lacking. In this study, Hsd3b7 was identified in the olive flounder Paralichthys olivaceus, an important mariculture fish. According to bioinformatics analysis, Hsd3b7 belongs to a Rossmann-fold NAD(P)(+)-binding protein and can interact in a predictable manner with Hsd17b2, -3, and - 4, which play a role in steroidogenesis. In the adult flounder, Hsd3b7 was expressed in various tissues, at particularly high level in male muscle. The expression levels of Hsd3b7 at gonadal development stages I-V initially increased and then decreased, with an inflection point in the ovary at stage III and in the testis at stage IV. At stage III, the expression level of Hsd3b7 was significantly higher in the ovary than in the testis (P < 0.01). The results of in situ hybridization (ISH) revealed that it was mainly expressed in oocytes of phases I-IV or around oocytes of phases IV-V in the ovaries and around spermatid lobules at stages IV-V in the testes. Three regulatory sites of SRY-box transcription factor 9 (Sox9), a transcription factor involved in steroidogenesis and gonadal differentiation, were predicted in the promoter of Hsd3b7. After intraperitoneal injection with the recombination flounder Sox9a, the expression of Hsd3b7 was significantly up-regulated (P < 0.01). During the flounder gonadal differentiation, 17β-estradiol (E2, 5 μg/g feed) and 17α-methyltestosterone (T, 5 μg/g feed) were used to obtain the phenotypic female or male flounder, and the results showed that in the E2 group, Hsd3b7 expression was highest at 2 cm TL, the primordial gonad stage, which was significantly higher than that at 12 cm TL (P < 0.05). In the T group, Hsd3b7 expression level was also highest at 2 cm TL and significantly higher than at 10 and 12 cm TL (P < 0.05). Moreover, Hsd3b7 was detected to be localized mainly around oogonia and spermatogonia during the differentiated gonads with ISH. These findings first introduce the expression characteristics of Hsd3b7 and the effect of Sox9a on its expression, which contribute to our understanding of the function of Hsd3b7 in fish gonads.
Topics: Animals; Female; Male; Flounder; Gene Expression Regulation, Developmental; Gonads; Mammals; Testis; Transcription Factors; Spermatogonia
PubMed: 36933762
DOI: 10.1016/j.cbpb.2023.110848 -
Journal of Ethnopharmacology Feb 2024Herba epimedium brevicornu maxim is traditionally known as a sexual enhancement, and has the effect of tonifying kidney yang. Icariin is a flavonoid extracted from...
ETHNOPHARMACOLOGICAL RELEVANCE
Herba epimedium brevicornu maxim is traditionally known as a sexual enhancement, and has the effect of tonifying kidney yang. Icariin is a flavonoid extracted from epimedium brevicornu maxim, and has been shown to improve nephropathy disease.
AIM OF THE STUDY
This study investigated the possible role of icariin in regulating renal EndMT in type 2 diabetic nephropathy (T2DN).
MATERIALS AND METHODS
Male type 2 diabetic Sprague Dawley rats, Male D2.BKS(D)-Leprdb/J (db/db) mice, and mouse glomerular endothelial cells were utilized to evaluate the effect of icariin. Western blotting, Q-PCR, immunohistochemistry, H&E, Masson staining, immunofluorescence, and siRNA transfection, were performed in this study.
RESULTS
The inhibitory function of icariin in renal fibrosis and renal EndMT was verified in type 2 diabetic animals. Methyltestosterone suppressed renal fibrosis and EndMT in db/db mice. Androgen receptor (AR), the major receptor of testosterone, was upregulated by icariin. The AR antagonist MDV3100, blocked the inhibition by icariin in renal EndMT, revealing that icariin repressed renal EndMT by activating AR. In addition, icariin and methyltestosterone upregulated the Raf kinase inhibitor protein (RKIP) in db/db mice. Furthermore, siRNA-RKIP inhibited the effect of icariin on EndMT. The MEK/ERK pathway, as the downstream pathway of RKIP, was suppressed by icariin and methyltestosterone. Of note, the effect of icariin on the MEK/ERK pathway was abolished by MDV3100 or siRNA-RKIP.
CONCLUSIONS
These results supported that icariin targeted AR/RKIP/MEK/ERK pathway to suppress renal fibrosis and EndMT in T2DN.
Topics: Rats; Male; Mice; Animals; Diabetic Nephropathies; Phosphatidylethanolamine Binding Protein; Endothelial Cells; Receptors, Androgen; Methyltestosterone; Rats, Sprague-Dawley; Flavonoids; Fibrosis; RNA, Small Interfering; Diabetes Mellitus, Type 2; Mitogen-Activated Protein Kinase Kinases; Epithelial-Mesenchymal Transition
PubMed: 37977422
DOI: 10.1016/j.jep.2023.117414