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2.
Prog Urol ; 30(10): 484-487, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32620366

RESUMO

COVID-19 is the pandemic that hit the world starting December 2019. Recent studies and international statistics have shown an increased prevalence, morbidity as well as mortality of this disease in male patients compared to female patients. The aim of this brief communication is to describe the pathophysiology of this sex-discrepancy, based on the infectivity mechanism of the coronavirus including the Angiotensin-Converting Enzyme 2 (ACE2), the Type II transmembrane Serine Protease (TMPRSS2), and the androgen receptor. This could help understand the susceptibility of urological patients, especially those receiving androgen deprivation therapy for prostate cancer, and testosterone replacement therapy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/etiologia , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/etiologia , Receptores Androgênicos/fisiologia , Receptores Virais/fisiologia , Serina Endopeptidases/fisiologia , Antagonistas de Androgênios/uso terapêutico , Androgênios/fisiologia , Antineoplásicos Hormonais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Especificidade de Órgãos , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Neoplasias da Próstata/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Sêmen/virologia , Serina Endopeptidases/biossíntese , Serina Endopeptidases/genética , Distribuição por Sexo , Glicoproteína da Espícula de Coronavírus/fisiologia , Internalização do Vírus
3.
Med Hypotheses ; 143: 110112, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721806

RESUMO

In coronavirus disease-19 (COVID-19), four major factors have been correlated with worse prognosis: aging, hypertension, obesity, and exposure to androgen hormones. Angiotensin-converting enzyme-2 (ACE2) receptor, regulation of the renin-angiotensin-aldosterone system (RAAS), and transmembrane serine protease 2 (TMPRSS2) action are critical for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry and infectivity. ACE2 expression and RAAS are abnormal in hypertension and obesity, while TMPRSS2 is overexpressed when exposed to androgens, which may justify why these factors are overrepresented in COVID-19. Among therapeutic targets for SARS-CoV-2, we hypothesized that spironolactone, a long used and safe mineralocorticoid and androgen receptors antagonist, with effective anti-hypertensive, cardioprotective, nephroprotective, and anti-androgenic properties may offer pleiotropic actions in different sites to protect from COVID-19. Current data shows that spironolactone may concurrently mitigate abnormal ACE2 expression, correct the balances membrane-attached and free circulating ACE2 and between angiotensin II and Angiotensin-(1-7) (Ang-(1-7)), suppress androgen-mediated TMPRSS2 activity, and inhibit obesity-related RAAS dysfunctions, with consequent decrease of viral priming. Hence, spironolactone may provide protection from SARS-CoV-2, and has sufficient plausibility to be clinically tested, particularly in the early stages of COVID-19.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/fisiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Espironolactona/uso terapêutico , Antagonistas de Androgênios/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Indução Enzimática/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Obesidade/complicações , Obesidade/fisiopatologia , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Prognóstico , Receptores Virais/efeitos dos fármacos , Fatores de Risco , Serina Endopeptidases/efeitos dos fármacos , Distribuição por Sexo , Espironolactona/farmacologia , Internalização do Vírus/efeitos dos fármacos
4.
Endocr Relat Cancer ; 27(9): R281-R292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32508311

RESUMO

The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/etiologia , Pneumonia Viral/etiologia , Neoplasias da Próstata/tratamento farmacológico , Androgênios/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/tratamento farmacológico , Serina Endopeptidases/fisiologia
5.
Sheng Li Xue Bao ; 72(2): 243-248, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328618

RESUMO

Androgen plays an important role in singing of songbirds. Recent studies have shown that androgen levels in vivo not only affect the external morphology of songbirds, but also affect their singing behavior. Androgens (including derivatives) affect singing behavior and singing system in many ways. Based mainly on the results from our research group in the zebra finch, this review summarizes the effects of androgen on singing behavior, excitability and synaptic transmission of projection neurons of singing system, and the interaction of androgen with other neurotransmitter receptors in the brain of songbirds.


Assuntos
Androgênios/fisiologia , Encéfalo/fisiologia , Aves Canoras/fisiologia , Vocalização Animal , Animais
6.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
7.
Andrologia ; 52(4): e13529, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32039514

RESUMO

Benign prostatic enlargement (BPE) is a disease that testosterone plays a role in its aetiology. Second to fourth finger ratio is a marker of prenatal androgenic exposure and may be a risk factor for several androgen-related diseases such as BPE. In this study, we investigated the relationship between the second to fourth finger ratio and BPE. A total of 63 patients with BPE were included for study group, and age-matched 63 healthy patients were included as a control group. Finger was measured by the distance from the proximal crease to the tip by using a digital caliper. The mean age of patients with BPE and non-BPE was 62 ± 8.9 and 61.5 ± 7.1 years respectively. There was statistically significant difference between groups in terms of prostate-specific antigen levels, prostate volumes and international prostate symptom scores. The mean finger ratios for right and left hand were 0.97 ± 0.03, 0.99 ± 0.03(p = .001) and 0.93 ± 0.15, 0.98 ± 0.03(p < .001) for BPE and non-BPE groups respectively. Men with a lower second to fourth finger ratio have higher risk of developing BPE than men without BPE. Therefore, the second to fourth finger ratio, which is indicative of prenatal androgen exposure, can be used as a marker of BPE risk.


Assuntos
Androgênios/fisiologia , Dedos/anatomia & histologia , Efeitos Tardios da Exposição Pré-Natal , Hiperplasia Prostática/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez
8.
Andrologia ; 52(3): e13521, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32003054

RESUMO

Down syndrome is the most common autosomal chromosome anomaly with several medical abnormalities and intellectual disability, occurring in about of 1:1,000 to 1:1,100 infants. Many pregnancies in women with Down syndrome produce children both with normal and with trisomy 21, whereas males are infertile. However, Down syndrome males are not always infertile and this is not global. Here we reported a 36-year-old man with proved nonmosaic trisomy 21 fathered two normal boys. Paternity analysis using 26 microsatellite loci confirmed that Down syndrome male is the biological father of his two normal boys. Serum LH, FSH, testosterone and 17-OH progesterone were all in the normal range in this father with Down syndrome. To the best of our knowledge, this is the second report of one man with Down syndrome who has two normal children in the world. The current study not only supports the rare evidence of the fertility of males with Down syndrome but also highlights the caution in advising people responsible for the care of adults with this condition about possible fertility and transmission of sexual diseases as well.


Assuntos
Androgênios/sangue , Síndrome de Down/fisiopatologia , Fertilidade/fisiologia , Paternidade , Adulto , Androgênios/fisiologia , Cromossomos Humanos Y/genética , Impressões Digitais de DNA , Síndrome de Down/sangue , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Humanos , Cariotipagem , Masculino , Repetições de Microssatélites/genética , Linhagem
9.
Ann Endocrinol (Paris) ; 80 Suppl 1: S29-S37, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31606059

RESUMO

PolyCystic Ovary Syndrome (PCOS) is the first endocrinopathy of women of child-bearing age and the leading cause of anovulatory infertility. The pathophysiology of this syndrome is complex and involves genetic traits highlighted by GWAS and epigenetic traits with DNA methylation modifications. Initially described as an ovarian disease, works carried out over recent years were turned towards neuroendocrine disorder involving GABAergic pathways, KNDy neurons and a possible role of prenatal androgen exposure determined by animal models. Clinically, PCOS leads to many complications including psychological and emotional disorders demonstrated in large populations of PCOS women. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.


Assuntos
Endocrinologia/tendências , Síndrome do Ovário Policístico , Androgênios/fisiologia , Endocrinologia/métodos , Endocrinologia/organização & administração , Epigênese Genética/fisiologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Transtornos Mentais/epidemiologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/terapia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia
10.
Front Horm Res ; 53: 18-32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31499499

RESUMO

Differences between males and females are commonly attributed to sexual hormones. Androgens are responsible for the development of primary and secondary sexual characteristics in males, whereas they influence sexual behaviour, glycaemic control, lipid profile, bone metabolism and erythropoiesis in both sexes. In this chapter, we discuss preclinical and clinical data on sex-specific androgen metabolism and androgen effect on body composition.


Assuntos
Androgênios/fisiologia , Composição Corporal/fisiologia , Caracteres Sexuais , Androgênios/metabolismo , Animais , Feminino , Humanos , Masculino
11.
Am J Physiol Renal Physiol ; 317(4): F996-F1009, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390231

RESUMO

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter "baseline" of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.


Assuntos
Androgênios/fisiologia , Próstata/anatomia & histologia , Próstata/fisiologia , Fenômenos Fisiológicos do Sistema Urinário , Inibidores de 5-alfa Redutase/farmacologia , Envelhecimento , Animais , Células Epiteliais/fisiologia , Feminino , Finasterida/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Orquiectomia , Próstata/citologia , Caracteres Sexuais , Testosterona/farmacologia , Fenômenos Fisiológicos do Sistema Urinário/efeitos dos fármacos , Fenômenos Fisiológicos do Sistema Urinário/genética , Urodinâmica
12.
Am J Physiol Endocrinol Metab ; 317(4): E631-E645, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361545

RESUMO

Androgen depletion in humans leads to significant atrophy of the limb muscles. However, the pathways by which androgens regulate limb muscle mass are unclear. Our laboratory previously showed that mitochondrial degradation was related to the induction of autophagy and the degree of muscle atrophy following androgen depletion, implying that decreased mitochondrial quality contributes to muscle atrophy. To increase our understanding of androgen-sensitive pathways regulating decreased mitochondrial quality, total RNA from the tibialis anterior of sham and castrated mice was subjected to microarray analysis. Using this unbiased approach, we identified significant changes in the expression of genes that compose the core molecular clock. To assess the extent to which androgen depletion altered the limb muscle clock, the tibialis anterior muscles from sham and castrated mice were harvested every 4 h throughout a diurnal cycle. The circadian expression patterns of various core clock genes and known clock-controlled genes were disrupted by castration, with most genes exhibiting an overall reduction in phase amplitude. Given that the core clock regulates mitochondrial quality, disruption of the clock coincided with changes in the expression of genes involved with mitochondrial quality control, suggesting a novel mechanism by which androgens may regulate mitochondrial quality. These events coincided with an overall increase in mitochondrial degradation in the muscle of castrated mice and an increase in markers of global autophagy-mediated protein breakdown. In all, these data are consistent with a novel conceptual model linking androgen depletion-induced limb muscle atrophy to reduced mitochondrial quality control via disruption of the molecular clock.


Assuntos
Androgênios/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Extremidades/fisiologia , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Animais , Atrofia , Autofagia , Peso Corporal , Extremidades/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitofagia , Músculo Esquelético/patologia , Orquiectomia , Testosterona/fisiologia , Tíbia/anatomia & histologia , Tíbia/crescimento & desenvolvimento
13.
Horm Behav ; 115: 104550, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31265826

RESUMO

The Challenge Hypothesis was developed to explain why and how regulatory mechanisms underlying patterns of testosterone secretion vary so much across species and populations as well as among and within individuals. The hypothesis has been tested many times over the past 30years in all vertebrate groups as well as some invertebrates. Some experimental tests supported the hypothesis but many did not. However, the emerging concepts and methods extend and widen the Challenge Hypothesis to potentially all endocrine systems, and not only control of secretion, but also transport mechanisms and how target cells are able to adjust their responsiveness to circulating levels of hormones independently of other tissues. The latter concept may be particularly important in explaining how tissues respond differently to the same hormone concentration. Responsiveness of the hypothalamo-pituitary-gonad (HPG) axis to environmental and social cues regulating reproductive functions may all be driven by gonadotropin-releasing hormone (GnRH) or gonadotropin-inhibiting hormone (GnIH), but the question remains as to how different contexts and social interactions result in stimulation of GnRH or GnIH release. These concepts, although suspected for many decades, continue to be explored as integral components of environmental endocrinology and underlie fundamental mechanisms by which animals, including ourselves, cope with a changing environment. Emerging mass spectrometry techniques will have a tremendous impact enabling measurement of multiple steroids in specific brain regions. Such data will provide greater spatial resolution for studying how social challenges impact multiple steroids within the brain. Potentially the Challenge Hypothesis will continue to stimulate new ways to explore hormone-behavior interactions and generate future hypotheses.


Assuntos
Androgênios/fisiologia , Comportamento Animal/fisiologia , Meio Ambiente , Neuroesteroides/metabolismo , Comportamento Social , Androgênios/metabolismo , Animais
14.
J Clin Invest ; 129(5): 1818-1826, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042159

RESUMO

Androgens and estrogens are known to be critical regulators of mammalian physiology and development. While these two classes of steroids share similar structures (in general, estrogens are derived from androgens via the enzyme aromatase), they subserve markedly different functions via their specific receptors. In the past, estrogens such as estradiol were thought to be most important in the regulation of female biology, while androgens such as testosterone and dihydrotestosterone were believed to primarily modulate development and physiology in males. However, the emergence of patients with deficiencies in androgen or estrogen hormone synthesis or actions, as well as the development of animal models that specifically target androgen- or estrogen-mediated signaling pathways, have revealed that estrogens and androgens regulate critical biological and pathological processes in both males and females. In fact, the concept of "male" and "female" hormones is an oversimplification of a complex developmental and biological network of steroid actions that directly impacts many organs. In this Review, we will discuss important roles of estrogens in males and androgens in females.


Assuntos
Androgênios/fisiologia , Estrogênios/fisiologia , Animais , Osso e Ossos/fisiologia , Neoplasias da Mama/patologia , Sistema Nervoso Central/fisiologia , Di-Hidrotestosterona , Progressão da Doença , Estradiol/fisiologia , Feminino , Genitália/fisiologia , Humanos , Masculino , Camundongos , Neoplasias da Próstata/patologia , Receptores Androgênicos/fisiologia , Receptores Estrogênicos/fisiologia , Fatores Sexuais , Testosterona/fisiologia
15.
Gynecol Endocrinol ; 35(8): 669-672, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31056990

RESUMO

Hyperandrogenism is one of the most common causes for anovulation in women and increases the risk for metabolic disorder in PCOS patients. Autophagy plays an important role in dysfunction of endocrine and anovulation. However, the relationship between hyperandrogenism and autophagy in human granulosa cells of PCOS patients remains unclear. By collecting granulosa cells from PCOS patients and non-PCOS patients, we found that the abundance of autophagy-related genes ATG5, ATG7, BECN1 mRNA and the ratio of autophagy marker protein light chain 3B II/I (LC3 II/I) were significantly increased whereas the abundance of the autophagy substrate SQSTM1/p62 was decreased in ovarian granulosa cells from PCOS patients. Furthermore, we demonstrated that BECN1 mRNA abundance in human granulosa cells positively correlated with the basal level of serum total testosterone and androgen up-regulated the abundance of BECN1 mRNA and the ratio of LC3II/LC3I in a dose-dependent manner in cultured granulosa cells. These observations indicated that androgen-induced activation of autophagy may play an important role in the development of PCOS and to explore the autophagy mechanisms involved in PCOS yield new insight into the pathophysiology and therapy of the disorder.


Assuntos
Androgênios/fisiologia , Autofagia/fisiologia , Células da Granulosa/fisiologia , Síndrome do Ovário Policístico/patologia , Adulto , Androgênios/metabolismo , Androgênios/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/genética , Estudos de Casos e Controles , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/metabolismo , Hiperandrogenismo/patologia , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Cultura Primária de Células , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-31047850

RESUMO

Autoimmune diseases (AIDs) are a heterogeneous group of disorders in terms of clinical manifestations, pathogenesis, and prevalence, and there is no agreement to date on a common classification. Adaptive immune responses are responsible for the existence of AIDs, although innate immunity is also involved in misguiding the immune response against self-antigens. Hormones, in general, and in particular steroid hormones, play a critical role in the physiology and pathology of the immune system, especially in adaptive immunity. Hormonal factors, alone or in relation to age, sex, and reproductive status, are involved in conditioning the onset of a number of AIDs. There is a well-defined sexual dimorphism for human AIDs. At the same time, the classic view has been that steroid hormones have well-defined effects, with one type, estrogens, being "pro-inflammatory" and the other two progestogens (progesterone and its synthetic analogs) and androgens being "anti-inflammatory." Although this view has been considered too simplistic and seems contradicted by numerous observations, it remains valid: progestogens and androgens are immunosuppressive and therefore protective against AIDs, whereas estrogens are immune-stimulatory and therefore pathogenic in AIDs.


Assuntos
Androgênios , Doenças Autoimunes , Estrogênios , Progesterona , Androgênios/fisiologia , Estrogênios/fisiologia , Humanos , Sistema Imunitário , Progesterona/fisiologia
17.
Endocr Rev ; 40(4): 1152-1162, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074764

RESUMO

Sex steroid estrogens, androgens, and progesterone, produced by the gonads, which have long been considered as endocrine glands, are implicated in sexual differentiation, puberty, and reproduction. However, the impact of sex hormones goes beyond these effects through their role on energy metabolism. Indeed, sex hormones are important physiological regulators of glucose homeostasis and, in particular, of the enteroinsular axis. In this review, we describe the roles of estrogens, androgens, and progesterone on glucose homeostasis through their effects on pancreatic α- and ß-cells, as well as on enteroendocrine L-cells, and their implications in hormonal biosynthesis and secretion. The analysis of their mechanisms of action with the dissection of the receptors implicated in the several protective effects could provide some new aspects of the fine-tuning of hormonal secretion under the influence of the sex. This knowledge paves the way to the understanding of transgender physiology and new potential therapeutics in the field of type 2 diabetes.


Assuntos
Androgênios/metabolismo , Células Enteroendócrinas/metabolismo , Glucose/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Progesterona/metabolismo , Androgênios/fisiologia , Animais , Trato Gastrointestinal/metabolismo , Células Secretoras de Glucagon/metabolismo , Hormônios Esteroides Gonadais/fisiologia , Humanos , Células Secretoras de Insulina/metabolismo , Camundongos , Progesterona/fisiologia , Ratos
18.
Syst Biol Reprod Med ; 65(4): 281-287, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30994373

RESUMO

The aim of the study was to determine if serum testosterone (T) and dehydroepiandrosterone (DHEAS) levels are a factor in determining increased risk for embryonic aneuploidy in karyotypically normal women undergoing in vitro fertilization (IVF) and preimplantation genetic testing screening for aneuploidy (PGT-A). This is a retrospective cohort study of IVF cycles with PGT-A performed during 2015-2016. A total of 256 cycles with 725 embryos were initially considered for inclusion. A total of 208 cycles and 595 embryos determined to be either euploid or aneuploid were included in the analysis. The mean age of women was 37.4 ± 4.4 years. There were 193 (32.44%) euploid, and 338 (56.81%) aneuploid blastocysts. Sixty-four (10.76%) had 'no diagnosis' after PGT-A. The 32 embryos with 'no diagnosis' after first PGT-A were biopsied again and after the second analysis, 7 were found to be euploid and 3 aneuploid. The remaining 32 embryos were not reanalyzed due to the lack of patients' consent for the second biopsy. The relationship between embryo ploidy and levels of serum testosterone and dehydroepiandrosterone sulfate was assessed using ordinal multivariable regression analysis. The model, adjusted for both anti-Mullerian hormone (AMH) and age, showed no association between ploidy status and serum levels of the two hormones. We concluded that the serum levels of testosterone and DHEAS do not influence embryo ploidy in karyotypically normal women undergoing IVF. Abbreviations: T: testosterone; DHEAS: dehydroepiandrosterone; IVF: in vitro fertilization; PGT-A: preimplantation genetic testing screening for aneuploidy; AMH: anti-Mullerian hormone; FSH: follicle-stimulating hormone; LH: luteinizing hormone; E2: oestradiol; P: progesterone.


Assuntos
Androgênios/fisiologia , Blastocisto/ultraestrutura , Ploidias , Adulto , Androgênios/sangue , Desidroepiandrosterona/sangue , Feminino , Fertilização In Vitro , Humanos , Cariótipo , Masculino , Gravidez , Fatores de Risco , Testosterona/sangue
19.
Med Hypotheses ; 126: 1-3, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31010486

RESUMO

Polycystic ovarian syndrome (PCOS) is an endocrine disorder characterized by alteration of menses, polycystic ovaries, clinical and or biochemical signs of hyper-androgenism in the context of metabolic abnormalities such as obesity and insulin resistance that play a fundamental role in pathogenesis of the disease as well as in development of long-term complications including cardiovascular disease (CVD) and type II diabetes mellitus (DM II). Latest evidence supports the hypothesis of a genetic component in the aetiology of PCOS that seems to be inherited through an oligo-genic mechanism and cluster in families. Recent studies identified the existence of a male PCOS correspondent syndrome in which the genes responsible for PCOS susceptibility in women may be inherited by male relatives of women with PCOS. The same hormonal, clinical and metabolic alterations of women with PCOS have been found in their male relatives suggesting a relation between the syndrome in its male equivalent. Considering clinical manifestations of male PCOS equivalent, the early onset andro-genetic alopecia (AGA) is considered a clinical marker of insulin resistance, supported by the findings of a case-control study that reported an increased prevalence of hyperinsulinemia and insulin-resistance-associated disorders such as dyslipidaemia, hypertension and obesity, in men with early onset of alopecia (<35), compared with age-matched controls. Moreover, AGA and insulin resistance show higher levels of active androgens, highlighting that low SHBG levels occur in both the diseases and that the two conditions may concur to a worsening of the disease. With regards to the existence of a male PCOS equivalent syndrome, in particular with refer to its phenotypic hallmark of early onset AGA, our hypothesis supposes a beneficial effect of diet restriction used for PCOS as therapy for male patients affected by PCOS equivalent syndrome. Several observational studies and some randomized trials reported that modest reductions of body weight decrease the risk of development of many diseases, including diabetes and cardiovascular disease and contributes to increase insulin sensitivity in PCOS women. Weight reduction may be adopted for men affected by PCOS equivalent syndrome in order to reduce both levels of circulating androgens, insulin resistance and related-complications such as CVD and DM II.


Assuntos
Alopecia/genética , Androgênios/fisiologia , Diabetes Mellitus Tipo 2/genética , Ciências da Nutrição , Síndrome do Ovário Policístico/genética , Adulto , Alopecia/etiologia , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/etiologia , Feminino , Predisposição Genética para Doença , Humanos , Resistência à Insulina , Masculino , Doenças Metabólicas/complicações , Pessoa de Meia-Idade , Modelos Biológicos , Fenótipo , Síndrome do Ovário Policístico/etiologia , Síndrome , Testosterona/fisiologia
20.
Arch. med. deporte ; 36(190): 101-108, mar. 2019. graf
Artigo em Inglês | IBECS | ID: ibc-186195

RESUMO

The aim of this review was to evaluate the current cognition about androgens (A) physiology, their pharmaceutical develo-pment and place in modern medicine. Special aspect was to explore the reasons and consequences of A use as so-called "lifestyle drugs" (LD). To write this review, we used the scientific papers in English of a recent date on PubMed, reference textbooks, books and monographs of different disciplines, as well as official documents and reports of some internationally recognized organizations (European Medicines Agency, World Anti-Doping Agency, Medicines and Healthcare products Regulatory Agency). Endocrinological role of A is generally known, but their non-hormonal effects are still the subject of intensive investigation. For decades, testosterone (T) and its esters have been the substitution therapy of the first choice in clearly defined clinical conditions. When it comes to pharmaceutical development, there are large number of effective and safe T formulations on the market which provide a very good patients’ compliance. Regarding clinical application of synthetic A with dominant anabolic activity, the only acceptable indication nowadays is severe burn injuries, while others have to be proven by high-quality clinical studies. Particularly worrying is the wide-spread use of anabolic steroids (AS) for non-medical purposes, as so-called LD. Although numerous and serious side-effects are well-documented, general impression is that both users of AS and clinicians should know more about the risks of their use. This review points to the need of better information and more comprehensive education at different levels, as well as implementation of additional preventive strategies, especially in the youth population, in order to avoid potentially serious consequences of the AS use


El objetivo de esta revisión fue evaluar el conocimiento actual sobre la fisiología de los andrógenos (A), su desarrollo farmacéutico y su lugar en la medicina moderna. Un aspecto especial fue estudiar las razones y consecuencias del uso de llamadas "medicamentos de estilo de vida" (LD).Para llevar a cabo esta revisión, se realizó una búsqueda de artículos científicos en inglés recientes en PubMed, libros y monografías de diferentes disciplinas, así como documentos oficiales e informes de algunas organizaciones reconocidas internacionalmente (Agencia Europea de Medicamentos, Agencia mundial Antidopaje, Agencia Reguladora de Medicamentos y Productos Sanitarios).El papel endocrinológico de los A es generalmente conocido, pero sus efectos no hormonales siguen siendo objeto de una investigación intensiva. Durante décadas, la testosterona (T ) y sus ésteres han sido la primera elección para terapia de sustitución en condiciones clínicas claramente definidas. Cuando se trata del desarrollo farmacéutico, hay una gran cantidad de formulaciones de T eficaces y seguras en el mercado que proporcionan un muy buen cumplimiento por parte de los pacientes. Con respecto a la aplicación clínica de A sintético con actividad anabólica dominante, la única indicación aceptable en la actualidad son las lesiones por quemaduras graves, mientras que otras deben ser probadas por estudios clínicos de alta calidad. Particularmente preocupante es el uso generalizado de los esteroides anabólicos (AS) para fines no médicos, como los llamados LD. Aunque los efectos secundarios son numerosos y graves, la impresión general es que tanto los usuarios de AS como los clínicos deberían saber más sobre los riesgos de su uso. Esta revisión apunta a la necesidad de una mejor información y una educación más integral en diferentes niveles, así como la implementación de estrategias preventivas adicionales, especialmente en la población joven, para evitar consecuencias potencialmente graves del uso de AS


Assuntos
Humanos , Androgênios/fisiologia , Androgênios/química , Testosterona/fisiologia , Medicina Baseada em Evidências , Terapia de Reposição Hormonal
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