Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.@*METHODS@#Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.@*RESULTS@#Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter -42 bp to -28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity / 亚洲男科学杂志(英文版)

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard / 亚洲男科学杂志(英文版)

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Attach great importance to the significance of serum anti-müllerian hormone and androgen in the evaluation of polycystic ovary syndrome / 中华预防医学杂志

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.

FOXA1 in prostate cancer / 亚洲男科学杂志(英文版)

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer / 亚洲男科学杂志(英文版)

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Síndrome de insensibilidad completa a andrógenos / Complete androgen insensitivity syndrome

El síndrome de insensibilidad a los andrógenos (SIA), conocido también como un síndrome de feminización testicular, incluye un grupo variado de mutaciones que se relacionan con la disfunción de los receptores de andrógenos y la resistencia de los tejidos diana a la acción de las hormonas masculinas. Es causado por alteraciones genéticas localizadas en la secuencia de codificación de los receptores de andrógenos ligada al cromosoma Xq11 - 12, el gen que codifica al receptor de los andrógenos, de un individuo genéticamente masculino (46 XY). Las formas clínicas moderada, parcial o completa, dependen del grado de insensibilidad androgénica. Los avances en las causas genéticas han permitido que estas condiciones congénitas de desarrollo del sexo cromosómico, gonadal o anatómico atípico sean denominados trastornos de diferenciación sexual

Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, includes a diverse group of mutations that are related to androgen receptor dysfunction and resistance of target tissues to the action of hormones masculine. It is caused by localized genetic alterations in the androgen receptor coding sequence linked to chromosome Xq11-12, the gene encoding the androgen receptor, of a genetically male (46 XY) individual. Moderate, partial, or complete clinical forms depend on the degree of androgen insensitivity. Advances in genetic causes have allowed these congenital conditions of atypical chromosomal, gonadal, or anatomical sex development to be called disorders of sexual differentiation

Classic and current concepts in adrenal steroidogenesis: a reappraisal

ABSTRACT Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a "mineralocorticoid (MC) pathway of zona fasciculata (ZF)", where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11β-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme - CYP11B1/CYP11B2 -, responsible for aldosterone formation in ZF under ACTH control, in "type I familial hyperaldosteronism" (dexamethasone suppressible). In "apparent MC excess syndrome", peripheral conversion of cortisol to cortisone is impaired by lack of 11β-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the "backdoor pathway", through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.

Complete androgen blockade vs. medical castration alone as adjuvant androgen deprivation therapy for prostate cancer patients following radical prostatectomy: a retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).@*METHODS@#Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.@*RESULTS@#A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60-1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14-1.00, P = 0.0497).@*CONCLUSION@#Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Testosterone levels in patients with varicocele and azoospermia / 北京大学学报(医学版)

OBJECTIVE@#Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level.@*METHODS@#Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL.@*RESULTS@#The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups (P < 0.001). The incidences had no difference between the VC and OA groups (P=0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [OR 0.492 (95% confidence interval 0.288-0.840)].@*CONCLUSION@#NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA).@*METHODS@#A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol.@*RESULTS@#The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case.@*CONCLUSION@#The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

Implante de testosterona para la mujer, evaluación de seguridad y efectividad en esta vía de administración / Testosterone implant for women, evaluation of safety and effectiveness in this route of administration

INTRODUCCIÓN Y OBJETIVO: El rol de la testosterona exógena en la función sexual femenina ha sido estudiado durante muchos años, con resultados contradictorios. En el último tiempo se ha promovido el uso de pellets de testosterona como una solución para mejorar la libido femenina, la cognición, la fuerza muscular y los sistemas cardiovascular y óseo, e incluso evitar el envejecimiento. Por ello, revisamos las publicaciones para tratar de responder si esto es una moda o el tratamiento más innovador del último tiempo. MÉTODO: Se analizaron las bases de datos PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct y ResearchGate. RESULTADOS: De acuerdo con la evidencia, la mejor testosterona disponible es la transdérmica y debe ser usada solo en el trastorno del deseo sexual hipoactivo (TDSH). Los trabajos que evalúan los pellets de testosterona tienen sesgos metodológicos importantes. Si bien son útiles para mejorar la función sexual femenina, producen concentraciones plasmáticas suprafisiológicas de testosterona, por lo que no se puede establecer su seguridad a largo plazo. Tampoco hay datos suficientes que avalen su uso para mejorar el rendimiento cognitivo y el bienestar general, en el tratamiento de enfermedades cardiovasculares o en la prevención de enfermedad ósea. CONCLUSIONES: La testosterona solo se recomienda en el tratamiento del TDSH por vía transdérmica. No recomendamos el uso de pellets de testosterona para el tratamiento de la disfunción sexual ni como hormona antienvejecimiento, ya que no hay estudios consistentes sobre su seguridad, eficacia y efectos adversos a largo plazo.

INTRODUCTION AND OBJECTIVE: The role of exogenous testosterone in female sexual function has been studied for many years with contradictory results. In recent times, the use of testosterone pellets has been promoted as a solution to improve female libido, cognition, muscle strength, cardiovascular system, bone and even prevent aging. Therefore, we will review the publications in order to answer whether this is a fad or the most innovative treatment of recent times. METHOD: The databases PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct and ResearchGate were analyzed. RESULTS: So far, the evidence best testosterone available is transdermal testosterone and that it should be used only in hypoactive sexual desire disorder (HSDD). Papers evaluating testosterone pellets have significant methodological biases. While they are useful in improving female sexual function, they produce supra-physiological plasma levels of testosterone, so their long-term safety cannot be established. There is also insufficient data to support their use in improving cognitive performance and general well-being, treatment of cardiovascular disease or prevention of bone disease. CONCLUSIONS: Testosterone is only recommended for the tratment of HSDD via the transdermal route. We do not recommended the use of testosterone pellets for the treatment of sexual dysfunction or as an anti aging hormone, as there are no consistent studies on its safety, efficacy, and long-term adverse effects.

The effect of androgen on wool follicles and keratin production in Hetian sheep / Efeito do androgênio na produção de folículos e queratina em ovinos Hetianos

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.

Lacrimal gland atrophy and dry eye related to isotretinoin, androgen, and prolactin: differential diagnosis for Sjögren's syndrome / Atrofia das glândulas lacrimais e olho seco relacionados aisotretinoína, androgênio e prolactina: diagnóstico diferencial com a síndrome de Sjögren

ABSTRACT This report is of three cases of sicca syndrome, initially suspected to be Sjögren's syndrome, which was ruled out by clinical and laboratory investigations. The patients were a 24-year-old woman, a 32-year-old man, and a 77-year-old woman with chronic symptoms of sicca syndrome, including dry eye syndrome. The first case was associated with the use of isotretinoin, a retinoic acid. The second was associated with the use of anabolic androgenic steroids, and the third was related to a prolactin- secreting pituitary adenoma. All cases manifested sicca, including dry eye syndrome, after those events, and the manifestations persisted. Magnetic resonance imaging revealed bilateral atrophy of the lacrimal gland. The medical history, ocular examinations, laboratory exams, and magnetic resonance images confirmed dry eye syndrome; however, the exams were all negative for Sjögren's syndrome. The lacrimal gland was absent on magnetic resonance imaging in all three cases. The clinical history revealed that the signs and symptoms appeared after chronic exposure to retinoic acid, anabolic androgenic steroids, and a prolactin-secreting pituitary adenoma, respectively. Chronic isotretinoin, anabolic androgenic steroids, and prolactin-secreting pituitary adenoma or, in this last case, its inhibitory treatment, can cause lacrimal gland atrophy, sicca syndrome, and dry eye syndrome, and a differential diagnosis of Sjögren's syndrome. Further studies on doses, time, and other susceptibilities to the long-lasting adverse effects of retinoic acid, anabolic androgenic steroids, and the repercussions of prolactin-secreting pituitary adenoma are necessary to confirm and expand upon these associations.

RESUMO O relato descreve três casos de síndrome de sicca, inicialmente suspeitos de serem a síndrome de Sjögren, que fo­ram negados pela investigação clínica e laboratorial. O primeiro associado ao uso de isotretinoína, um ácido retinóico, o segundo ao uso de esteroides androgênicos anabolizantes e o terceiro relacionado ao adenoma da hipófise secretora da prolactina, todos manifestaram sicca, incluindo a síndrome do olho seco após esses eventos e as manifestações persistem. A ressonância magnética revelou atrofia bilateral da glândula lacrimal. Eles eram uma mulher de 24 anos, um homem de 32 anos e uma mulher de 77 anos com sintomas crônicos da síndrome de sicca, incluindo a síndrome do olho seco. A história médica, o exame ocular, os exames laboratoriais e a ressonância magnética foram confirmados como síndrome do olho seco, no entanto, todos os exames foram negativos para a síndrome de Sjögren. A glândula lacrimal estava ausente na ressonância magnética nos três casos. A história clínica revelou que sinais e sintomas se manifestaram após exposição crônica ao ácido retinóico, esteróides anabolizantes androgênicos e adenoma secretivo da prolactina hipofisária, respectivamente. Isotretinoína crônica, esteroides anabólicos androgênicos e adenoma hipofisário secretor de prolactina ou, neste último caso, seu tratamento inibitório pode ser a causa da atrofia da glândula lacrimal, síndrome da sicca e síndrome do olho seco e diagnóstico diferencial da síndrome de Sjögren. Estudos adicionais sobre doses, duração e outras suscetibilidades aos efeitos adversos duradouros do ácido retinóico, esteroides androgênicos anabólicos e repercussões do adenoma da hipófise secretora da prolactina são necessários para confirmar e detalhar essas associações.

Suplementación de testosterona durante el climaterio en mujeres con trastorno por deseo sexual hipoactivo / Testosterone supplementation during the climacteric period in women with hypoactive sexual desire disorder

A partir del caso de una paciente con trastorno por deseo sexual hipoactivo durante su climaterio y a través del resumen de los resultados de dos revisiones sistemáticas, los autores de este artículo revisan la evidencia sobre la suplementación con andrógenos para el tratamiento de esta condición clínica. Concluyen que su uso sería relativamente seguro a corto plazo, aunque su eficacia no alcanzaría la relevancia clínica y no contamos aún con mayor información sobre la seguridad en el largo plazo. Los autores destacan además que el abordaje de las pacientes con este problema de salud debería ser realizado en forma integral, incluyendo opciones terapéuticas no farmacológicas e informando sobre las incertidumbres todavía presentes. (AU)

Based on the case of a patient with hypoactive sexual desire disorder during her climacteric period and through the summary of the results of two systematic reviews, the authors of this article review the evidence supporting androgen supplementation for the treatment of this clinical condition. They conclude that its use would be relatively safe in the short term, although its efficacy would not reach clinical relevance and no further information on long-term safety is available. The authors also highlight that patients with this health problem should be approached comprehensively, including non-pharmacological therapeutic options and providing information on the uncertainties still present. (AU)

Masculinization in common carp (Cyprinus carpio) by androgen immersion: The interaction effect of hormone concentration and immersion time / Masculinização na carpa comum (Cyprinus carpio) por imersão em androgênio: Efeito da interação da concentração hormonal e do tempo de imersão

Synthetic androgens (male hormones) administered to fish nursery are being used in aquaculture to avoid sexual differentiation and unwanted spawning at the eggs or the first feeding fry stage of fish. Present trial was conducted with the aim to produce male common carp (Cyprinus carpio) by egg immersion technique. Through this little insight, the effect of different hormone concentrations (17α-methyltestosterone @ HC:150, 300, 450 and 600 µgl-1) with immersion times (IT: 24, 48 and 72 hrs) and their interaction effect (HC x IT) on the hatching percentage of Cyprinus carpio eggs, percent survival and percent of male's production was evaluated specifically. Results showed that egg hatching percentage decreased with increased IT likewise, survival of treated fry was affected by increasing the IT (P<0.001). The main interaction effect of HC x IT showed that the highest percent of male individuals (95%) was obtained at 450-600 µgl-1 HC for 72 hrs IT, followed by 88-92.50% at 150-300 µgl-1 HC for 72-hrsof IT, 87.50% at 48-hrs of IT for rest of the hormone treatments, and lowest 47.50% was recorded in control (P<0.05). Increased percent male of Cyprinus carpio was obtained with increasing HC across all ITs. It was observed that the immersion treatment at 600µgl-1 for 72 hours was more effective to change the sex ratio of pre hatch Cyprinus carpio. A comparative outlook made from this experimental trial that sex induction of Cyprinus carpio by eggs immersion using synthetic male steroid hormone is an alternative safe technique of fish sex reversal in contrast to oral administration of hormone in fish feed.

Andrógenos sintéticos (hormônios masculinos) administrados ao viveiro de peixes estão sendo usados ​​na aquicultura para evitar a diferenciação sexual e a desova indesejada nos ovos ou no primeiro estágio de alimentação dos peixes. O presente estudo foi conduzido com o objetivo de produzir carpa comum masculina (Cyprinuscarpio) pela técnica de imersão em ovos. Com essa pequena percepção, o efeito de diferentes concentrações hormonais (17α-metiltestosterona @ HC: 150, 300, 450 e 600 µgl-1) com tempos de imersão (IT: 24, 48 e 72 horas) e seu efeito de interação (HC x IT) na porcentagem de eclosão dos ovos de Cyprinuscarpio, a porcentagem de sobrevivência e a porcentagem da produção masculina foram avaliadas especificamente. Os resultados mostraram que a porcentagem de incubação de ovos diminuiu com o aumento da TI da mesma forma, a sobrevivência dos alevinos tratados foi afetada pelo aumento da TI (P <0,001). O principal efeito de interação do HC x IT mostrou que o maior percentual de indivíduos do sexo masculino (95%) foi obtido com 450-600 µgl-1 HC por 72 horas de TI, seguido por 88-92,50% com 150-300 µgl-1 HC para 72 horas de TI, 87,50% às 48 horas de TI para o restante dos tratamentos hormonais, e 47,50% mais baixos foram registrados no controle (P <0,05). A porcentagem aumentada de macho de Cyprinuscarpio foi obtida com o aumento do HC em todas as TIs. Observou-se que o tratamento de imersão a 600µgl-1 por 72 horas foi mais efetivo na alteração da razão sexual do Cyprinuscarpio antes da eclosão. Uma perspectiva comparativa feita a partir deste ensaio experimental de que a indução sexual de Cyprinuscarpio por imersão de ovos usando hormônio esteróide masculino sintético é uma técnica alternativa segura de reversão do sexo em peixes, em contraste com a administração oral de hormônio na alimentação de peixes.