Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.576
Filtrar
1.
Molecules ; 26(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672087

RESUMO

Testosterone derivatives and related compounds (such as anabolic-androgenic steroids-AAS) are frequently misused by athletes (both professional and amateur) wishing to promote muscle development and strength or to cover AAS misuse. Even though these agents are vastly regarded as abusive material, they have important pharmacological activities that cannot be easily replaced by other drugs and have therapeutic potential in a range of conditions (e.g., wasting syndromes, severe burns, muscle and bone injuries, anemia, hereditary angioedema). Testosterone and related steroids have been in some countries treated as controlled substances, which may affect the availability of these agents for patients who need them for therapeutic reasons in a given country. Although these agents are currently regarded as rather older generation drugs and their use may lead to serious side-effects, they still have medicinal value as androgenic, anabolic, and even anti-androgenic agents. This review summarizes and revisits the medicinal use of compounds based on the structure and biological activity of testosterone, with examples of specific compounds. Additionally, some of the newer androgenic-anabolic compounds are discussed such as selective androgen receptor modulators, the efficacy/adverse-effect profiles of which have not been sufficiently established and which may pose a greater risk than conventional androgenic-anabolic agents.


Assuntos
Esteroides/uso terapêutico , Testosterona/uso terapêutico , Animais , Drogas Desenhadas/química , Drogas Desenhadas/uso terapêutico , Humanos , Plantas/química , Pró-Fármacos/química , Pró-Fármacos/uso terapêutico , Esteroides/química , Testosterona/agonistas , Testosterona/análogos & derivados , Testosterona/química
2.
J Sex Med ; 18(3): 646-655, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33531255

RESUMO

BACKGROUND: While the effects of androgens on muscle are well described in hypogonadal men, literature is still scarce on muscular strength or size variations in transmen; in this population there are no data regarding the relative effect of testosterone (T) and its metabolite dihydrotestosterone on muscle. AIM: Our primary objective was to compare the effects on muscle strength of 54-week administration of testosterone undecanoate (TU) combined with the 5α-reductase inhibitor dutasteride (DT) or placebo (PL). Secondary outcomes included evaluation of body composition, bone, cutaneous androgenic effects, and metabolic variations. METHODS: In this randomized, double-blind PL-controlled pilot trial, 16 ovariectomized transmen were randomized to receive TU 1,000 mg IM at week 0, 6, 18, 30, 42 plus a PL pill orally daily (TU + PL, n = 7) or plus DT 5 mg/d (TU + DT, n = 7). OUTCOMES: At week 0 and 54 the following parameters were evaluated: isokinetic knee extension and flexion peak torque and handgrip strength, body composition, and bone mineral density, biochemical, hematological, and hormonal parameters. RESULTS: Handgrip and lower limb strength increased significantly in both groups with no differences between the 2 groups. Fat mass decreased and lean mass increased significantly similarly in both groups. Metabolic parameters remained stable in the 2 groups except for high-density lipoprotein cholesterol that was reduced in both groups. Hepatic and renal function remained normal in both groups and no major adverse effects were registered in either group. CLINICAL IMPLICATIONS: These results may be particularly relevant for transmen experiencing cutaneous androgenic adverse events such as acne and androgenetic alopecia and in light of the development of non-5α-reduced androgens. STRENGTHS & LIMITATIONS: The strength of this study was the randomized, double-blind PL-controlled design, while the small number of subjects was definitely the biggest limitation. CONCLUSION: For the first time we demonstrated that the addition of DT does not impair the anabolic effects of T on muscles in transmen previously exposed to T, supporting the hypothesis that the conversion in dihydrotestosterone is not essential for this role. Gava G, Armillotta F, Pillastrini P, et al. A Randomized Double-Blind Placebo-Controlled Pilot Trial on the Effects of Testosterone Undecanoate Plus Dutasteride or Placebo on Muscle Strength, Body Composition, and Metabolic Profile in Transmen. J Sex Med 2021;18:646-655.


Assuntos
Força da Mão , Metaboloma , Composição Corporal , Método Duplo-Cego , Dutasterida/uso terapêutico , Humanos , Masculino , Força Muscular , Projetos Piloto , Testosterona/análogos & derivados
3.
Eur J Endocrinol ; 184(3): 353-363, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33444228

RESUMO

Objective: Androgens are important modulators of immune cell function. The local generation of active androgens from circulating precursors is an important mediator of androgen action in peripheral target cells or tissues. We aimed to characterize the activation of classic and 11-oxygenated androgens in human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were isolated from healthy male donors and incubated ex vivo with precursors and active androgens of the classic and 11-oxygenated androgen pathways. Steroids were quantified by liquid chromatography-tandem mass spectrometry. The expression of genes encoding steroid-metabolizing enzymes was assessed by quantitative PCR. Results: PBMCs generated eight-fold higher amounts of the active 11-oxygenated androgen 11-ketotestosterone than the classic androgen testosterone from their respective precursors. We identified the enzyme AKR1C3 as the major reductive 17ß-hydroxysteroid dehydrogenase in PBMCs responsible for both conversions and found that within the PBMC compartment natural killer cells are the major site of AKRC13 expression and activity. Steroid 5α-reductase type 1 catalyzed the 5α-reduction of classic but not 11-oxygenated androgens in PBMCs. Lag time prior to the separation of cellular components from whole blood increased serum 11-ketotestosterone concentrations in a time-dependent fashion, with significant increases detected from two hours after blood collection. Conclusions: 11-Oxygenated androgens are the preferred substrates for androgen activation by AKR1C3 in PBMCs, primarily conveyed by natural killer cell AKR1C3 activity, yielding 11-ketotestosterone the major active androgen in PBMCs. Androgen metabolism by PBMCs can affect the results of serum 11-ketotestosterone measurements, if samples are not separated in a timely fashion. Significance statement: We show that human peripheral blood mononuclear cells (PBMCs) preferentially activate 11-ketotestosterone rather than testosterone when incubated with precursors of both the classic and the adrenal-derived 11-oxygenated androgen biosynthesis pathways. We demonstrate that this activity is catalyzed by the enzyme AKR1C3, which we found to primarily reside in natural killer cells, major contributors to the anti-viral immune defense. This potentially links intracrine 11-oxygenated androgen generation to the previously observed decreased NK cell cytotoxicity and increased infection risk in primary adrenal insufficiency. In addition, we show that PBMCs continue to generate 11-ketotestosterone if the cellular component of whole blood samples is not removed in a timely fashion, which could affect measurements of this active androgen in routine clinical biochemistry.


Assuntos
Membro C3 da Família 1 de alfa-Ceto Redutase/metabolismo , Androgênios/metabolismo , Leucócitos Mononucleares/metabolismo , Cromatografia Líquida , Humanos , Masculino , Espectrometria de Massas em Tandem , Testosterona/análogos & derivados , Testosterona/metabolismo
4.
Molecules ; 26(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466340

RESUMO

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo.


Assuntos
Fragaria/química , Intestino Delgado/metabolismo , Sistema Linfático/metabolismo , Extratos Vegetais/administração & dosagem , Testosterona/análogos & derivados , Testosterona/metabolismo , Administração Oral , Adulto , Disponibilidade Biológica , Células CACO-2 , Humanos , Hidrólise , Intestino Delgado/efeitos dos fármacos , Sistema Linfático/efeitos dos fármacos , Masculino
5.
Am J Clin Oncol ; 44(4): 137-142, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33512910

RESUMO

BACKGROUND: Fatigue is one of the most common adverse events of systemic therapy in patients with metastatic renal cell carcinoma (RCC). The aim of multicenter randomized phase 2 study was to determine the efficacy and safety of testosterone in patients with fatigue developed during targeted therapy. PATIENTS AND METHODS: Male patients with metastatic clear-cell RCC, normal prostate-specific antigen level, low testosterone level, and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either testosterone undecanoate (1000 mg) and targeted therapy or targeted therapy alone. The primary endpoint was the mean change of fatigue from baseline to 28 days according to the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary endpoints were safety, Functional Assessment of Cancer Therapy-Kidney Symptom Index 19, testosterone serum concentrations, red blood cell count, and hemoglobin level. RESULTS: Sixty patients were assigned to receive testosterone and targeted therapy (N=30) or targeted therapy alone (N=30). As of the data cutoff on December 30, 2019, median follow-up was 18.2 months. The study achieved its primary endpoint based on the significant differences at day 28 favoring testosterone over targeted therapy alone regarding the decreased level of fatigue (difference between groups, 22.5 points; 95% confidence interval, 18.4-26.6; P=0.012). Significant changes in scores demonstrating the enhanced quality of life with testosterone compared with targeted therapy were also observed for Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 disease-related symptoms (P=0.01). There were nonsignificant differences in red blood cell count and hemoglobin level between the 2 groups (all P>0.05). CONCLUSION: Male patients with metastatic RCC and hypogonadism receiving testosterone had less fatigue and better symptom control during targeted therapy.


Assuntos
Carcinoma de Células Renais/secundário , Fadiga/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Testosterona/análogos & derivados , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Fadiga/etiologia , Fadiga/psicologia , Seguimentos , Humanos , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Qualidade de Vida , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico , Testosterona/efeitos adversos , Testosterona/uso terapêutico
6.
J Steroid Biochem Mol Biol ; 205: 105774, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33172831

RESUMO

Conjugation with glucuronic acid is one of the major metabolic reactions in human steroid hormone catabolism. Recently, increasing interest has been raised concerning the biological roles of steroid glucuronides. We have therefore developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 15 urinary steroid hormone glucuronides in human urine: androsterone glucuronide (An-G), etiocholanolone glucuronide (Etio-G), epiandrosterone glucuronide (epiAn-G), dihydrotestosterone glucuronide (DHT-G), dehydroepiandrosterone glucuronide (DHEA-G), testosterone glucuronide (T-G), epitestosterone glucuronide (epiT-G), estrone glucuronide (E1-3 G), 17ß-estradiol 17-glucuronide (E2-17 G), 17ß-estradiol 3-glucuronide (E2-3 G), estriol 16-glucuronide (E3-16 G), pregnenolone glucuronide (Preg-G), tetrahydro-11-deoxycorticosterone 3-glucuronide (THDOC-3 G), cortisol 21-glucuronide (F-G) and pregnanediol glucuronide (PD-G). Sample workup included protein precipitation and solid phase extraction. Internal standards were used to correct for the loss of analytes during sample preparation and analysis. The method showed good linearity (R2≥0.99) and recovery ranged from 89.6 % to 113.8 %. Limit of quantification ranged from 1.9 nmol/L for F-G to 21.4 nmol/L for An-G. Intra-day and inter-day accuracy and precision were below 15 % for all quality controls. The method was successfully applied to 67 urine samples from children and adolescents in whom total concentrations of free and conjugated steroids had been previously determined by GC-MS after enzymatic hydrolysis. Free and sulfated steroids were also measured by LC-MS/MS. In general, the sums of the respective glucuronidated, sulfated and free forms of an analyte corresponded well with its total amount determined after enzymatic hydrolysis by GC-MS. Regarding the most prominent steroid metabolites, the total mean levels of androsterone and etiocholanolone showed an increase up to 5820.0 nmol/L and 4017.8 nmol/L in the group of 15-20 year-old children, respectively. Glucuronide conjugates (4374.3 nmol/L and 3588.5 nmol/L, respectively) dominated. DHEA was excreted mostly as sulfate (0-1 month of age: 184.5 nmol/L; 15-20 years of age: 1618.4 nmol/L) in all age groups. Cortisol was present predominantly as sulfate (mean: 173.8 nmol/L) in newborns. Levels of sulfated cortisol decreased with age, its glucuronidated form increased. The levels of free cortisol were relatively constant throughout childhood. Sex hormones were preferably excreted as glucuronides. In general, steroid hormone metabolites were conjugated to various extents with glucuronic acid or sulfuric acid and their ratio changed over lifetime.


Assuntos
Androsterona/análogos & derivados , Glucuronídeos/urina , Hormônios Esteroides Gonadais/urina , Testosterona/análogos & derivados , Androsterona/química , Androsterona/urina , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucuronídeos/química , Hormônios Esteroides Gonadais/química , Humanos , Masculino , Extração em Fase Sólida , Esteroides/química , Esteroides/urina , Espectrometria de Massas em Tandem , Testosterona/química , Testosterona/urina
7.
Zhonghua Nan Ke Xue ; 26(4): 346-350, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33351303

RESUMO

Objective: To evaluate the efficacy and safety of Jiarong Tablets (JRT) combined with Testosterone Undecanoate Capsules (TUC) in the treatment of late-onset hypogonadism (LOH) in males. METHODS: This randomized open multicentered clinical trial included 200 cases of LOH meeting the inclusion, which were equally randomized into a control (aged ï¼»51.09 ± 5.6ï¼½ yr) and a trial group (aged ï¼»50.46 ± 5.2ï¼½ yr) to be treated with oral TUC (40 mg, bid) and TUC+JRT (0.92 g, tid) respectively for 12 successive weeks. We obtained the Aging Males' Symptoms (AMS) and IIEF-5 scores, serum total testosterone (TT) content, red blood cell (RBC) count, hepatic and renal function indexes and glucose and total PSA levels before and after treatment, and compared them between the two groups of patients. RESULTS: Totally, 191 of the LOH patients completed the experiment, 95 in the control and 96 in the trial group. After 12 weeks of treatment, the patients in the trial group, compared with the controls, showed significant improvement in the AMS score (20.6 ± 5.7 vs 31.9 ± 6.1, P < 0.05), IIEF-5 score (20.3 ± 3.1 vs 16.3 ± 3.8, P < 0.05) and serum TT level (ï¼»16.1 ± 3.9ï¼½ vs ï¼»12.7 ± 3.4ï¼½ nmol/L, P < 0.05). There were no significant adverse events or abnormalities in the RBC count, hepatic and renal functions, or glucose and total PSA levels in the two groups of patients before and after medication. CONCLUSIONS: JRT combined with TUC is safe and effective and superior to TUC alone in the treatment of LOH in males.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hipogonadismo , Testosterona/análogos & derivados , Adulto , Cápsulas , Humanos , Hipogonadismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Comprimidos , Testosterona/uso terapêutico , Resultado do Tratamento
8.
J Vis Exp ; (166)2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33369605

RESUMO

Sex steroids, produced by the gonads, play an essential role in brain and pituitary tissue plasticity and in the neuroendocrine control of reproduction in all vertebrates by providing feedback to the brain and pituitary. Teleost fishes possess a higher degree of tissue plasticity and variation in reproductive strategies compared to mammals and appear to be useful models to investigate the role of sex steroids and the mechanisms by which they act. The removal of the main source of sex steroid production using gonadectomy together with blood sampling to measure steroid levels has been well-established and fairly feasible in bigger fish and is a powerful technique to investigate the role and effects of sex steroids. However, these techniques raise challenges when implemented in small size teleost models. Here, we describe the step-by-step procedures of gonadectomy in both males and female Japanese medaka followed by blood sampling. These protocols are shown to be highly feasible in medaka indicated by a high survival rate, safety for the life span and phenotype of the fish, and reproducibility in terms of sex steroid clearance. The use of these procedures combined with the other advantages of using this small teleost model will greatly improve the understanding of feedback mechanisms in the neuroendocrine control of reproduction and tissue plasticity provided by sex steroids in vertebrates.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Tamanho Corporal , Castração , Oryzias/anatomia & histologia , Oryzias/sangue , Animais , Castração/instrumentação , Estradiol/sangue , Feminino , Gônadas/cirurgia , Masculino , Modelos Animais , Oviposição , Reprodutibilidade dos Testes , Suturas , Testosterona/análogos & derivados , Testosterona/sangue
9.
Eur J Endocrinol ; 183(5): 529-536, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33071222

RESUMO

Objective: Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change. Design and methods: Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage. Results: A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01-1.83 per SD increase in LH). Conclusions: There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Composição Corporal , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Testosterona/uso terapêutico , Pessoas Transgênero , Adulto , Distribuição da Gordura Corporal , Acetato de Ciproterona/uso terapêutico , Relação Dose-Resposta a Droga , Impedância Elétrica , Estradiol/sangue , Feminino , Humanos , Hormônio Luteinizante/sangue , Masculino , Medicina de Precisão , Procedimentos de Readequação Sexual/métodos , Testosterona/análogos & derivados , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
J Steroid Biochem Mol Biol ; 202: 105724, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32629108

RESUMO

Testosterone and its 5α-reduced form, 5α-dihydrotestosterone, were previously thought to represent the only active androgens in humans. However, recent studies have shown that the potent androgen, 11-ketotestosterone, derived from the adrenal androgen precursor, 11ß-hydroxyandrostenedione, may in fact serve as the primary androgen in healthy women. Yet, despite recent renewed interest in these steroids, their downstream metabolism has remained undetermined. We therefore set out to investigate the metabolism of 11-ketotestosterone by characterising the 5α- or 5ß-reduction commitment step. We show that inactivation of 11-ketotestosterone is predominantly driven by AKR1D1, which efficiently catalyses the 5ß-reduction of 11-ketotestosterone, committing it to a metabolic pathway that terminates in 11-ketoetiocholanolone. We demonstrate that 5α-reduction of 11-ketotestosterone is catalysed by SRD5A2, but not SRD5A1, and terminates in 11-ketoandrosterone, but is only responsible for a minority of 11-ketotestosterone inactivation. However, as 11-ketoetiocholanolone is also generated by the metabolism of the glucocorticoid cortisone, 11-ketoandrosterone should be considered a more specific urinary marker of 11-ketotestosterone production.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Proteínas de Membrana/metabolismo , Oxirredutases/metabolismo , Testosterona/análogos & derivados , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Catálise , Linhagem Celular Tumoral , Cortisona/metabolismo , Feminino , Humanos , Fígado/metabolismo , Proteínas de Membrana/genética , Oxirredução , Oxirredutases/genética , Testosterona/metabolismo
12.
Adv Gerontol ; 33(2): 385-390, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32593257

RESUMO

There are changes in the metabolism, reproductive and nervous systems with ageing, which have a systemic and interrelated nature. The purpose of this work was to demonstrate the effectiveness of audiovisual correction and therapy with testosterone drugs in addition to the standard therapy in patients with polymorbid pathology. 89 men aged 35-55 years old with diabetes mellitus, polymorbid cardiovascular disease, obesity, anxiety and depressive disorders were examined. They were divided into 3 groups depending on the treatment: the 1st - standard therapy and escitalopram / tofisopam; the 2nd - standard therapy + audiovisual correction; the 3rd - standard therapy + audiovisual correction + testosterone undecanoate. Laboratory examination was carried out in all patients before the start of treatment and 9 months after the treatment. The severity of androgen deficiency was determined using IIEF-5 questionnaire and the AMS male aging scale. In was shown a decrease in testosterone levels, signs of erectile dysfunction and symptoms of moderate to severe androgen deficiency, increased proatherogenic and decreased antiatherogenic lipoproteins, increased glucose, glycated hemoglobin, insulin, HOMA index in our study. In group of audiovisual correction we saw a more significant improvement in the lipid profile after treatment. Audiovisual correction and androgen therapy contributed to the improvement of erectile function indices and a decrease in the severity of the symptoms of ageing in men.


Assuntos
Senilidade Prematura/prevenção & controle , Androgênios/uso terapêutico , Recursos Audiovisuais , Terapia de Reposição Hormonal , Idoso , Androgênios/deficiência , Androgênios/farmacologia , Disfunção Erétil/terapia , Humanos , Masculino , Ereção Peniana/efeitos dos fármacos , Testosterona/análogos & derivados , Testosterona/farmacologia , Testosterona/uso terapêutico
18.
PLoS One ; 15(2): e0229391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092110

RESUMO

Our previous work documented significant advancements in steroid-induced progression of oogenesis, demonstrating that co-treatment of female eels with 11-ketotestosterone (11KT) and estradiol-17ß (E2) successfully induced uptake of vitellogenin by oocytes. Here we evaluate the effects of this steroid co-treatment on subsequent time to ovulation and egg quality in shortfinned eels artificially matured by hypophysation. Co-treatment with 11KT (1 mg) and E2 (0.2 or 2 mg) significantly reduced time to ovulation and therefore, the amount of pituitary homogenate required, without any detrimental effects on gonadosomatic index, oocyte diameter or the total weight of stripped eggs. E2 treatment resulted in promising increases in fertilization rates. These indicators suggest that co-treatment with 11KT and E2 holds promise for future artificial maturation practices in terms of minimising fish handling and stress, and of reducing the need for expensive pituitary preparations.


Assuntos
Anguilla , Estradiol/farmacologia , Oogênese/efeitos dos fármacos , Indução da Ovulação , Testosterona/análogos & derivados , Anguilla/fisiologia , Animais , Feminino , Fertilidade/efeitos dos fármacos , Oócitos/citologia , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Oogênese/fisiologia , Ovário/citologia , Ovário/efeitos dos fármacos , Indução da Ovulação/métodos , Indução da Ovulação/veterinária , Testosterona/farmacologia
19.
Gen Comp Endocrinol ; 291: 113404, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001324

RESUMO

The role of gonadotropins during early ovarian development in fish remains little understood. Concentrations of gonadotropins were therefore experimentally elevated in vivo by administration of recombinant follicle-stimulating hormone (rec-Fsh) or human chorionic gonadotropin (hCG) and the effects on ovarian morphology, sex steroid levels and mRNA levels of genes expressed in pituitary and ovary examined. Hormones were injected thrice at weekly intervals in different doses (20, 100 or 500 µg/kg BW for rec-Fsh and 20, 100 or 500 IU/kg BW for hCG). All treatments, especially at the highest doses of either rec-Fsh or hCG, induced ovarian development, reflected in increased oocyte size and lipid uptake. Both gonadotropins up-regulated follicle-stimulating hormone receptor (fshr) mRNA levels and plasma levels of estradiol-17ß (E2). Exogenous gonadotropins largely decreased the expression of follicle-stimulating hormone ß-subunit (fshb) and had little effect on those of luteinizing hormone ß-subunit (lhb) in the pituitary. It is proposed that the effects of hCG on ovarian development in previtellogenic eels could be indirect as a significant increase in plasma levels of 11-ketotestosterone (11-KT) was found in eels treated with hCG. Using rec-Fsh and hCG has potential for inducing puberty in eels in captivity, and indeed, in teleost fish at large.


Assuntos
Anguilla/crescimento & desenvolvimento , Oócitos/metabolismo , Testosterona/análogos & derivados , Vitelogeninas/metabolismo , Anguilla/genética , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aromatase/genética , Aromatase/metabolismo , Gonadotropina Coriônica/farmacologia , Família 11 do Citocromo P450/genética , Família 11 do Citocromo P450/metabolismo , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Hormônios Esteroides Gonadais/genética , Hormônios Esteroides Gonadais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Testosterona/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-32109748

RESUMO

The standard approach to detect misuse with testosterone in sport is based on the determination and evaluation of the urinary steroid profile followed by the confirmation of atypical profiles using isotope ratio mass spectrometry. The detection capacity of these methods can be attenuated by confounding factors or testosterone preparations with endogenous isotopic fingerprints. An alternative detection method for misuse of an endogenous steroid in sports is the direct detection of the administered steroid ester present in most preparations. Thus unambiguous proof for doping misuse can be delivered. In this work, the sensitivity of gas chromatography coupled to a triple quadrupole with chemical ionization (GC-CI-MS/MS) is applied to detect trace levels of 10 testosterone and 2 nandrolone esters in plasma for in human doping analysis. The detection method was developed employing a liquid-liquid extraction and HPLC cleanup step before analysis on the GC-CI-MS/MS. The quantitative method was validated in a linear range of 100-2000 pg/ml and proved to be selective, reproducible and very sensitive with limits of detection as low as to 10 pg/ml. A clinical study with the administration of testosterone undecanoate in 3 volunteers was carried out and the compound was detectable up to 86 days after administration.


Assuntos
Doping nos Esportes , Cromatografia Gasosa-Espectrometria de Massas/métodos , Esteroides/sangue , Espectrometria de Massas em Tandem/métodos , Ésteres , Humanos , Modelos Lineares , Extração Líquido-Líquido , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Esteroides/química , Esteroides/isolamento & purificação , Testosterona/análogos & derivados , Testosterona/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...