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Proceedings of the Royal Society of... Feb 1973
Topics: Adolescent; Adult; Age Factors; Aged; Blood Pressure; Castration; Climacteric; Endometrial Hyperplasia; Estradiol; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Hysterectomy; Libido; Male; Medroxyprogesterone; Menopause; Methyltestosterone; Middle Aged; Norethindrone; Osteoporosis; Progesterone
PubMed: 4351701
DOI: No ID Found -
Fertility and Sterility Apr 2002Bone health and strength are dependent on the coupling of cone resorption and bone formation. This process is governed by the interaction of osteoclasts and osteoblasts... (Review)
Review
Bone health and strength are dependent on the coupling of cone resorption and bone formation. This process is governed by the interaction of osteoclasts and osteoblasts plus the modulating influence of the bone mechanicosensory cells-the osteocytes. Both sex steroids-estrogen (E) and testosterone (T)- have receptors on all bone cells, with androgen dominance on osteoblasts and osteocytes. Specific receptors for the weaker androgens, such as DHEA have also been identified. The activity of the sex steroids, influenced by various enzymes found in bone, is reflective of the hormone ligand before its binding to the bone cells. As a result, T acts both directly and via its aromatization to estradiol. The activity of the androgens also varies with the bone surface; periosteal cells, for example, do not have 5alpha-reductase activity, indicating that T is the active metabolite at this clinically important site. Androgens influence bone cell function via local and systemic growth factors and cytokines. By enhancing osteoblast differentiation, androgens regulate bone matrix production, organization, and mineralization. Androgens also regulate osteoclast recruitment and activity. Endogenous androgens increase bone mineral density (BMD) in both adolescent and adult premenopausal women. Women with excess endogenous androgen-for example, those with hirsutism and polycystic ovary syndrome (PCOS)-have increased BMD compared with normal young women. E and androgen therapy increases BMD to a greater degree than does E therapy alone. This is true for both oral combinations of esterified E and methyltestosterone and for subcutaneous T implants. Androgenic progestins have an additive effect on BMD when combined with E therapy and have the further advantage of being protective to the endometrium in E-treated women. Androgens increase muscle mass and strength. The resulting improvement in physical activity leads to the activation of bone-forming sites and the stimulation of the bone formation-modulating cells, the osteocytes. Mechanical loading, when combined with hormone therapy, results in greater osteogenic response than does either alone.
Topics: Androgens; Animals; Bone Density; Bone Remodeling; Bone and Bones; Estrogens; Female; Humans; Muscles; Osteoblasts; Osteoclasts; Receptors, Androgen; Receptors, Estrogen
PubMed: 12007900
DOI: 10.1016/s0015-0282(02)02968-0 -
BMC Genomics Jul 2017Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal...
BACKGROUND
Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. Androgens and aromatase inhibitors can induce female-to-male sex reversal, however, the mechanisms underlying gonadal masculinisation are poorly understood. We used histological analyses together with RNA sequencing to characterise zebrafish gonadal transcriptomes and investigate the effects of 17α-methyltestosterone on gonadal differentiation.
RESULTS
At a morphological level, 17α-methyltestosterone (MT) masculinised gonads and accelerated spermatogenesis, and these changes were paralleled in masculinisation and de-feminisation of gonadal transcriptomes. MT treatment upregulated expression of genes involved in male sex determination and differentiation (amh, dmrt1, gsdf and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and hsd11b2). It also repressed expression of ovarian development and folliculogenesis genes (bmp15, gdf9, figla, zp2.1 and zp3b). Furthermore, MT treatment altered epigenetic modification of histones in zebrafish gonads. Contrary to expectations, higher levels of cyp19a1a or foxl2 expression in control ovaries compared to MT-treated testes and control testes were not statistically significant during early gonad development (40 dpf).
CONCLUSION
Our study suggests that both androgen production and aromatase inhibition are important for androgen-induced gonadal masculinisation and natural testicular differentiation in zebrafish.
Topics: Animals; Female; Male; Methyltestosterone; Ovary; Sex Characteristics; Sex Ratio; Spermatogenesis; Testis; Transcriptome; Zebrafish
PubMed: 28738802
DOI: 10.1186/s12864-017-3915-z -
The Journal of Steroid Biochemistry and... Sep 2024Methyltestosterone (MT) is one of the most frequently misused anabolic androgenic steroids detected in doping control analysis. The metabolism of MT in humans leads to...
Methyltestosterone (MT) is one of the most frequently misused anabolic androgenic steroids detected in doping control analysis. The metabolism of MT in humans leads to several phase І metabolites and their corresponding phase Ⅱ conjugates. Previous studies have postulated the 3α-sulfoconjugate of 17α-methyl-5β-androstane-3α,17β-diol (S2) as principal sulfate metabolite of MT, with a detection window exceeding 10 days. However, a final direct and unambiguous confirmation of the structure of this metabolite is missing until now. In this study, we established an approach to detect and identify S2, using intact analysis by liquid chromatography hyphenated with tandem mass spectrometry (LC-MS/MS) without complex sample pretreatment. An in vitro study yielded the LC-MS/MS reference retention times of all 3-sulfated 17-methylandrostane-3,17-diol diastereomers, allowing for accurate structure assignment of potentially detected metabolites. In an in vivo excretion study with a single healthy male volunteer, the presence of the metabolite S2 was confirmed after a single oral dose of 10 mg MT. The reference standard was chemically synthesized, characterized by accurate mass mass spectrometry (MS) and nuclear magnetic resonance (NMR), and quantified by quantitative NMR (qNMR). Thus, this study finally provides accurate structure information on the S2 metabolite and a direct analytical method for detection of MT misuse. The availability of the reference material is expected to facilitate further evaluation and subsequent analytical method validation in anti-doping research.
Topics: Male; Humans; Methyltestosterone; Tandem Mass Spectrometry; Chromatography, Liquid; Substance Abuse Detection; Doping in Sports; Anabolic Agents; Adult; Liquid Chromatography-Mass Spectrometry
PubMed: 38710312
DOI: 10.1016/j.jsbmb.2024.106527 -
International Journal of Molecular... Feb 202317α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ...
17α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ cell maturation in . To further investigate the regulation of gonadal development by MT through the hypothalamic-pituitary-gonadal (HPG) axis, were exposed to 0, 25, 50, and 100 ng/L of MT for 7, 14, and 21 days. We analyzed its biological indicators, gonadotropin-releasing hormone (GnRH), gonadotropins, reproduction-related gene expression, and brain tissue transcriptome profiles. We found a significant decrease in the gonadosomatic index (GSI) in males exposed to MT for 21 days compared to the control group. GnRH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, as well as the expressions of the , , , , and genes, were significantly reduced in the brains of both male and female fish when exposed to 100 ng/L MT for 14 days compared to the controls. Therefore, we further constructed four RNA-seq libraries from 100 ng/L MT-treated groups of male and female fish, obtaining 2412 and 2509 DEGs in male and female brain tissue, respectively. Three common pathways were observed to be affected in both sexes after exposure to MT, namely, nicotinate and nicotinamide metabolism, focal adhesion, and cell adhesion molecules. Furthermore, we found that MT affected the PI3K/Akt/FoxO3a signaling pathway through the upregulation of and , and the downregulation of and . Therefore, we hypothesize that MT interferes with the levels of gonadotropin-releasing hormone (GnRH, FSH, and LH) in brains through the PI3K/Akt/FoxO3a signaling pathway, and affects the expression of key genes in the hormone production pathway (, and ) to interfere with the stability of the HPG axis, thus leading to abnormal gonadal development. This study provides a multidimensional perspective on the damaging effects of MT on fish and confirms that is a suitable model animal for aquatic toxicology.
Topics: Animals; Female; Male; Methyltestosterone; Transcriptome; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Cyprinidae; Gonadal Steroid Hormones; Cypriniformes; Brain; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone
PubMed: 36834982
DOI: 10.3390/ijms24043571 -
British Medical Journal Jan 1959
Topics: Jaundice; Methyltestosterone; Testosterone
PubMed: 13618612
DOI: 10.1136/bmj.1.5117.259 -
American Journal of Hematology Nov 2004The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review... (Review)
Review
The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review were as follows: (1) androgen-treated individuals who do not have FA are also at risk of liver tumors; (2) parenteral as well as oral androgens may be responsible for liver tumors; (3) FA patients develop liver tumors after smaller and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic neoplasms may depend on the specific androgen. Medline and Web of Science were searched for all cases of liver tumors associated with androgens. Information from individual cases was entered into a spreadsheet and descriptive statistical analyses were performed. Thirty-six FA cases and 97 non-FA cases with both nonhematologic disorders and acquired aplastic anemia (non-FA AA) were identified. The most common androgens were oxymetholone, methyltestosterone, and danazol. Hepatocellular carcinomas (HCC) were more often associated with oxymetholone and methyltestosterone, while adenomas were associated with danazol. Tumors were reported in six patients who received only parenteral and not oral androgens. FA patients were younger than non-FA patients when androgen use was initiated, and the FA patients developed tumors at younger ages. Non-AA patients were treated with androgens for longer periods of time, compared with FA and non-FA AA patients. All patients on anabolic androgenic steroids are at risk of liver tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be determined from currently available data, because the number of patients receiving androgens is unknown.
Topics: Adenoma, Liver Cell; Adult; Aged; Anabolic Agents; Androgens; Anemia, Aplastic; Carcinoma, Hepatocellular; Danazol; Estrogen Antagonists; Fanconi Anemia; Female; Humans; Liver Neoplasms; Male; Methyltestosterone; Middle Aged; Neoplasms, Hormone-Dependent; Oxymetholone; Risk Factors
PubMed: 15495253
DOI: 10.1002/ajh.20183 -
Regulatory mechanism of LncRNAs in gonadal differentiation of hermaphroditic fish, Monopterus albus.Biology of Sex Differences Oct 2023Monopterus albus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism...
BACKGROUND
Monopterus albus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism of the sex reversal was unknown.
METHODS
We produced transcriptomes containing mRNAs and lncRNAs in the crucial stages of the gonad, including the ovary, ovotestis and testis. The expression of the crucial lncRNAs and their target genes was detected using qRT‒PCR and in situ hybridization. The methylation level and activity of the lncRNA promoter were analysed by applying bisulfite sequencing PCR and dual-luciferase reporter assays, respectively.
RESULTS
This effort revealed that gonadal development was a dynamic expression change. Regulatory networks of lncRNAs and their target genes were constructed through integrated analysis of lncRNA and mRNA data. The expression and DNA methylation of the lncRNAs MSTRG.38036 and MSTRG.12998 and their target genes Psmβ8 and Ptk2β were detected in developing gonads and sex reversal gonads. The results showed that lncRNAs and their target genes exhibited consistent expression profiles and that the DNA methylation levels were negatively regulated lncRNA expression. Furthermore, we found that Ptk2β probably regulates cyp19a1 expression via the Ptk2β/EGFR/STAT3 pathway to reprogram sex differentiation.
CONCLUSIONS
This study provides novel insight from lncRNA to explore the potential molecular mechanism by which DNA methylation regulates lncRNA expression to facilitate target gene transcription to reprogram sex differentiation in M. albus, which will also enrich the sex differentiation mechanism of teleosts.
Topics: Male; Animals; Female; RNA, Long Noncoding; Gonads; Ovary; Testis; Sex Differentiation; Smegmamorpha
PubMed: 37880697
DOI: 10.1186/s13293-023-00559-y