Hipoplasia testicular em bovinos: causas e consequências / Testicular hypoplasia in cattle: causes and consequences

A hipoplasia testicular ocorre na maioria dos animais domésticos, sendo caracterizada pela ausência ou diminuição do desenvolvimento do epitélio germinativo dos túbulos seminíferos. Apesar de nem todas as causas da hipoplasia testicular estarem completamente elucidadas, pode-se destacar as gênicas, as cromossômicas e as ambientais. A manifestação mais comum da hipoplasia gonadal clássica é de origem congênita e de caráter hereditário, determinada por um gene autossômico recessivo de penetrância incompleta. Apesar dos relatos de frequência serem escassos, essa patologia é descrita em quase todas as raças bovinas. Em rebanhos com alto grau de consanguinidade ou com uso intensivo de reprodutores homozigotos recessivos para a patologia, podem ocorrer manifestações em 5 a 15% dos animais. Nos casos de hipoplasia testicular, causada por genes recessivos de penetrância incompleta, tais genes podem passar para as gerações seguintes, causando subfertilidade tanto em machos como em fêmeas, sendo recomendada a eliminação de animais clinicamente suspeitos por assimetria testicular ou por baixo padrão de circunferência escrotal para a idade e peso. Touros com hipoplasia unilateral ou parcial são animais azoospérmicos ou oligospérmicos, porém quadros moderados a leves podem não estar associados a problemas de qualidade seminal, possibilitando que touros assintomáticos transmitam genes indesejáveis às próximas gerações. O estabelecimento de critérios rígidos de verificação de aspectos clínico-andrológicos é imprescindível para um diagnóstico precoce e para a seleção preliminar de reprodutores bovinos. As avaliações genômicas são caminhos promissores para mapear e identificar os principais marcadores associados à expressão gênica da hipoplasia testicular, com sua possível aplicação para seleção de touros de elite.(AU)

Testicular hypoplasia occurs in most domestic animals and is characterized by the absence or decreased development of the germinative epithelium of the seminiferous tubules. Although not all causes of testicular hypoplasia are elucidated, we can highlight the genetic, chromosomal and environmental causes. The manifestation of the most common classic gonadal hypoplasia is from congenital causes, determined by an autosomal recessive gene of incomplete penetrance. Although reports of frequency are scarce, this pathology is described in almost all bovine breeds. In herds with a high degree of inbreeding or intensive use of subfertile bulls, manifestations may occur in 5% to 15% of the animals. In cases of testicular hypoplasia, caused by recessive genes of incomplete penetrance, such genes can pass on to the following generations, causing subfertility in both males and females, being recommended the elimination of animals clinically suspected by testicular asymmetry or by low standard of scrotal circumference for age and weight. Bulls with unilateral or partial hypoplasia are azoospermic or oligospermic, however moderate conditions may not be associated with seminal quality problems, allowing asymptomatic bulls to spread undesirable genes to the next generations. The establishment of strict criteria for checking clinical and andrological aspects is essential for an early diagnosis and preliminary Bull's selection. Genomic evaluation is a promising way to map and identify the main genetic markers associated with testicular hypoplasia expression genes and its use for bull's selection.(AU)

Hipoplasia testicular em bovinos: causas e consequências / Testicular hypoplasia in cattle: causes and consequences

A hipoplasia testicular ocorre na maioria dos animais domésticos, sendo caracterizada pela ausência ou diminuição do desenvolvimento do epitélio germinativo dos túbulos seminíferos. Apesar de nem todas as causas da hipoplasia testicular estarem completamente elucidadas, pode-se destacar as gênicas, as cromossômicas e as ambientais. A manifestação mais comum da hipoplasia gonadal clássica é de origem congênita e de caráter hereditário, determinada por um gene autossômico recessivo de penetrância incompleta. Apesar dos relatos de frequência serem escassos, essa patologia é descrita em quase todas as raças bovinas. Em rebanhos com alto grau de consanguinidade ou com uso intensivo de reprodutores homozigotos recessivos para a patologia, podem ocorrer manifestações em 5 a 15% dos animais. Nos casos de hipoplasia testicular, causada por genes recessivos de penetrância incompleta, tais genes podem passar para as gerações seguintes, causando subfertilidade tanto em machos como em fêmeas, sendo recomendada a eliminação de animais clinicamente suspeitos por assimetria testicular ou por baixo padrão de circunferência escrotal para a idade e peso. Touros com hipoplasia unilateral ou parcial são animais azoospérmicos ou oligospérmicos, porém quadros moderados a leves podem não estar associados a problemas de qualidade seminal, possibilitando que touros assintomáticos transmitam genes indesejáveis às próximas gerações. O estabelecimento de critérios rígidos de verificação de aspectos clínico-andrológicos é imprescindível para um diagnóstico precoce e para a seleção preliminar de reprodutores bovinos. As avaliações genômicas são caminhos promissores para mapear e identificar os principais marcadores associados à expressão gênica da hipoplasia testicular, com sua possível aplicação para seleção de touros de elite.

Testicular hypoplasia occurs in most domestic animals and is characterized by the absence or decreased development of the germinative epithelium of the seminiferous tubules. Although not all causes of testicular hypoplasia are elucidated, we can highlight the genetic, chromosomal and environmental causes. The manifestation of the most common classic gonadal hypoplasia is from congenital causes, determined by an autosomal recessive gene of incomplete penetrance. Although reports of frequency are scarce, this pathology is described in almost all bovine breeds. In herds with a high degree of inbreeding or intensive use of subfertile bulls, manifestations may occur in 5% to 15% of the animals. In cases of testicular hypoplasia, caused by recessive genes of incomplete penetrance, such genes can pass on to the following generations, causing subfertility in both males and females, being recommended the elimination of animals clinically suspected by testicular asymmetry or by low standard of scrotal circumference for age and weight. Bulls with unilateral or partial hypoplasia are azoospermic or oligospermic, however moderate conditions may not be associated with seminal quality problems, allowing asymptomatic bulls to spread undesirable genes to the next generations. The establishment of strict criteria for checking clinical and andrological aspects is essential for an early diagnosis and preliminary Bull's selection. Genomic evaluation is a promising way to map and identify the main genetic markers associated with testicular hypoplasia expression genes and its use for bull's selection.

Hormonas sexuales en la enfermedad crítica / Sexual hormones in critical disease

INTRODUCCIÓN. En el paciente crítico ha existido un conglomerado de situaciones dadas por alteración de las hormonas acorde al comportamiento del eje hipotalámi-co-hipofisario- gonadal, entender su rol es fundamental. OBJETIVO. Describir las alteraciones de las hormonas sexuales en el paciente críticamente enfermo desde un enfoque fisiológico y clínico. MATERIALES Y MÉTODOS. Estudio observacional, de revisión bibliográfica y análisis sistemático de 84 artículos científicos y selección de muestra de 27 en MedLine, The Cochrane Library Plus, LILACS y Web of Science; en español e inglés y variables: hormonas esteroides gonadales, enfermedad crítica, endocrinología, estrés, gónadas y disfunción, periodo 1998-2017. CONCLUSIÓN. Las alteraciones detectadas fueron un mecanismo para la producción de hormonas esteroideas hacia la síntesis predominante de cortisol y soportar el alto estrés meta-bólico de los pacientes. Las citocinas pro inflamatorias fueron importantes en éstos cambios. La polifarmacia fue un factor adicional poco ponderado de la alteración endocrina sexual.

INTRODUCTION. In the critical patient there has been a conglomerate of situations given by alteration of the hormones according to the behavior of the hypothalamic-pi-tuitary-gonadal axis, understanding their role is fundamental. OBJECTIVE. Describe the alterations of sex hormones in the critically ill patient from a physiological and clinical approach.MATERIALS AND METHODS.Observational, literature review and systematic analysis of 84 scientific articles and sample selection of 27 in MedLine, The Cochrane Library Plus, LILACS and Web of Science; in Spanish and English and variables: gonadal steroid hormones, critical illness, endocrinology, stress, gonads and dysfunction, period 1998-2017. CONCLUSION. The alterations detected were a mechanism for the production of steroid hormones towards the predominant syn-thesis of cortisol and withstand the high metabolic stress of the patients. Pro inflam-matory cytokines were important in these changes. Polypharmacy was an additional unweighted factor of sexual endocrine disruption.

Síndrome de Turner: nuestra experiencia en la creación del Registro Institucional y de la Unidad Interdisciplinaria en el Hospital Italiano de Buenos Aires: un primer paso para el mejor seguimiento / Turner syndrome: our experience in the creation of the Registry Institutional and Interdisciplinary Unit at the Italian Hospital of Buenos Aires: a first step to the best follow-up

El síndrome de Turner (ST) resulta de la ausencia completa o parcial del segundo cromosoma sexual en fenotipos femeninos. Tiene una incidencia de 1:2000- 2500 nacidas vivas. Recién en la última década se ha puesto atención a la salud de las adultas con ST. La mortalidad es 3 veces superior respecto de la población general debido al riesgo de disección aórtica por anomalías cardiovasculares estructurales y aterosclerosis vinculada a hipertensión arterial, diabetes, dislipidemia y obesidad. También presentan elevada prevalencia de enfermedades autoinmunitarias. Objetivo: evaluar la calidad del seguimiento clínico de pacientes adultas con ST, comparando los controles de salud preconformación y posconformación del Registro y de la Unidad Interdisciplinaria. En el año 2017 fuimos convocados para integrar el Programa de Enfermedades Raras del Hospital Italiano de Buenos Aires. A partir de la creación del Registro Institucional y del equipo multidisciplinario obtuvimos mejoría significativa en los controles por las especialidades de cardiología, endocrinología y otorrinolaringología, en los controles bioquímicos del metabolismo lipídico, hidrocarbonado, hepatograma, TSH y anticuerpos para celiaquía e imágenes cardiovasculares y densitometría ósea. En conclusión, el seguimiento sistematizado e institucional, mediante el Registro y la creación de la Unidad Interdisciplinaria de Síndrome de Turner, permitió encontrar las falencias del sistema de atención y optimizar el seguimiento de esta población. (AU)

Turner syndrome (TS) results from the complete or partial absence of the second sex chromosome in female phenotypes. It has an incidence of 1: 2000-2500 girls born alive. Only in the last decade has been paid attention to the health of adults women with TS. Mortality is 3 times higher than in the general population due to the risk of aortic dissection cause to structural cardiovascular anomalies and atherosclerosis related to hypertension, diabetes, dyslipidemia and obesity. They also have a high prevalence of autoimmune diseases. Until nowadays in Argentina do not exist a national registry of this disease that complies with the international follow-up recommendations for these patients. We proposed to develop the institutional register at 2014 and a multidisciplinary team was created to care and follow up girls and women with TS during 2015. It was indexed to Italian Hospital of Buenos Aires' Rare Diseases Program since 2017. After the creation of the institutional registry and the multidisciplinary team we obtained a significant improvement in cardiology, endocrinology and otorhinolaryngology schedule visits, in lipids and hydrocarbon metabolism, liver, thyroid and celiac diseases biochemical controls and in the performance of cardiovascular MNR and bone densitometry. In conclusion, the systematized and institutional follow-up, through the registry and the creation of the Interdisciplinary Unit of Turner Syndrome, allowed us to find the flaws of the care system and to optimize the follow up of this population. (AU)

Función gonadal en niños y adolescentes nacidos con restricción del crecimiento intrauterino / Gonadal function in children and adolescents born with restriction of intrauterine growth

Los niños con restricción del crecimiento intrauterino (RCIU) presentan en la vida posnatal una serie de alteraciones metabólicas y hormonales, y tienen predisposición al desarrollo de obesidad, hipertensión arterial, enfermedad cardiovascular, resistencia a la insulina y diabetes tipo 2. La exposición a un ambiente intrauterino desfavorable en fases críticas del desarrollo puede tener un efecto deletéreo sobre la gónada en formación. Se realizó una revisión bibliográfica y puesta al día sobre la posible asociación entre RCIU y alteraciones de la función gonadal en niños y adolescentes de ambos sexos. Para facilitar la actualización, se dividió por etapas en: 1, prenatal; 2, posnatal y prepuberal; 3, puberal, y 4, adulta. La mayoría de los niños que nacen muy prematuros o con muy bajo peso al nacer hacen una transición sin obstáculos desde la infancia a la edad adulta con respecto a la salud reproductiva. Sin embargo, en los varones se puede observar criptorquidia, hipospadias, cáncer testicular y menor fertilidad, y en las niñas, pubertad y menarca temprana, hiperandrogenismo y síndrome de ovario poliquístico. Existen datos controvertidos y se necesitan más estudios para aclarar la relación entre el RCIU y la función hipotálamo-hipófiso-gonadal.

Low birth weight due to intrauterine growth restriction (IUGR) is associated with an increased risk of obesity, hypertension, cardiovascular disease, insulin resistance, and type 2 diabetes during postnatal life. Exposure to an unfavourable intrauterine environment in critical phases of development may have a deleterious effect on the forming gonad. The objective was to carry out a bibliographic review and update on the possible association between IUGR and alterations of gonadal function in children and adolescents of both sexes. To facilitate the update, this was divided into stages: 1, prenatal; 2, postnatal and pre-pubertal; 3, puberal, and 4, adult. Most children born preterm or with low birth weight make a normal transition from childhood to adulthood with respect to reproductive health. However, cryptorchidism, hypospadias, testicular cancer and lower fertility could be observed in boys, and early puberty and menarche, hyperandrogenism and polycystic ovarian syndrome in girls. However, the data are controversial, and further studies are needed to clarify the relationship between IUGR and pituitary gonadal function.

Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals.

Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309-320, 2016. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.

Intratesticular and intraovarian epidermoid inclusion cysts: report of two cases / Cistos de inclusão epidérmica intratesticular e intraovariano: relato de dois casos

Two rare cases of intragonadal epidermoid inclusion cysts are described. Their etiology remains controversial and a possible hypothesis is monodermal abortive teratomas, with no mesodermal and endodermal components. As the ultrasound test results were inconclusive, it became difficult to rule out the possibility of neoplasm. Therefore, patients were submitted to radical therapy. The definitive diagnosis for both cases was provided by the anatomopathological examination.

Trata-se de dois casos raros de cistos de inclusão epidérmica intragonadais, cuja etiologia permanece controversa, sendo uma hipótese a de teratomas monodérmicos abortivos, sem componentes mesodérmicos e endodérmicos. Devido a resultados inespecíficos dos exames ultrassonográficos, torna-se difícil afastar a possibilidade de neoplasia e o tratamento padrão permanece sendo, portanto, a terapia radical. O diagnóstico definitivo, em ambos os casos, foi firmado pelo exame anatomopatológico.

Protección gonadal de pacientes con malignidades hematológicas durante la quimioterapia: uso del acetato de leuprolide / Gonadal protection in patients with hematological malignancies during chemotherapy: use of leuprolide acetate

Demostrar el papel de los análogos agonistas de hormona liberadora de gonadotropinas en la reserva ovárica de pacientes hemato-oncológicas del Servicio de Hematología del Hospital Universitario de Caracas durante el año 2010, en tratamiento con regímenes de quimioterapia. Estudio de la variable reserva ovárica, mediante la cuantificación periódica de: ritmo menstrual, concentraciones de FSH, volumen ovárico, número de folículos antrales e incidencia de embarazo. Se administró acetato de leuprolide (11,25 mg) cada 3 meses vía intramuscular; se realizaron mediciones trimestrales de las concentraciones de FSH y se practicaron ecosonogramas pélvico o transvaginal cada 6 meses. Posterior al cumplimiento de los análogos de la hormona liberadora de gonadotropinas, se observó la aparición de amenorrea en las pacientes. Las concentraciones de FSH se mantuvieron estables, y siguieron la misma distribución (prueba de Levene p 0,2466) los volúmenes ováricos y el número de folículos antrales se mantienen estables, se rechaza la hipótesis de normalidad del grupo de diferencias al 5 por ciento de significancia. No se registraron embarazos. La reserva ovárica se preserva durante el tratamiento continuo con análogos

To demonstrate the role gonadotropin releasing hormone analogues in ovarian reserve in hematology patients in the hematology service at the Hospital Universitario de Caracas in 2010, treated with chemotherapy regimens. Study of ovarian reserve variable by periodic quantification of: menstrual rhythm, concentrations of FSH, ovarian volume, antral follicle number and incidence of pregnancy. Leuprolide acetate was administered (11.25 mg) intramuscularly every 3 months, were measured quarterly and FSH concentrations were performed pelvic or transvaginal ecosonograms every 6 months. After aGnRH administration, we observed the occurrence of amenorrhea in patients. FSH concentrations were stable, and followed the same distribution (Levene test p 0.2466) ovarian volume and antral follicle numbers were stable, we reject the hypothesis of normality of group differences at 5 percent significance. There were no pregnancies. Ovarian reserve is preserved during continuous treatment with analogs

Inhibin B and anti-Müllerian hormone as markers of gonadal function after treatment for medulloblastoma or posterior fossa ependymoma during childhood.

OBJECTIVE: To evaluate the roles of hypothalamic-pituitary and spinal irradiations and chemotherapy in gonadal deficiency after treatment for medulloblastoma or posterior fossa ependymoma by measuring levels of plasma inhibin B and antimüllerian hormone (AMH). STUDY DESIGN: A total of 34 boys and 22 girls were classified as having normal levels of plasma follicle-stimulating hormone (FSH; <9 IU/L), or abnormal levels of FSH (>9 IU/L) and luteinizing hormone (LH; <5 or >5 IUL). RESULTS: Two boys had partial gonadotropin deficiency, combined with testicular deficiency in one boy. Six boys had increased levels of FSH, indicating tubular deficiency, combined with Leydig cell deficiency in 5 boys. The 7 boys with inhibin B levels <100 ng/mL included the one with combined deficiencies and the 6 with testicular deficiency. Puberty did not progress in 7 girls; 3 had gonadotropin deficiency, combined with ovarian deficiency in one, and 4 had increased FSH levels, indicating ovarian deficiency. Inhibin B and AMH levels were low in the girl with combined deficiencies, in the 4 girls with ovarian deficiency, and in 4 girls with normal clinical-biological ovarian function, including 2 who underwent ovarian transposition before irradiation. CONCLUSION: The plasma concentrations of inhibin B and AMH are useful means of detecting primary gonad deficiency in patients with no increase in their plasma gonadotropin levels because of radiation-induced gonadotropin deficiency.

Detección precoz de trastornos endocrinológicos / Early detection of endocrinological disorders

Se revisan los trastornos más comunes del sistema endocrino que se detectan en la consulta no especializada. Se hace énfasis en: a) Trastornos tiroideos tales como hipo o hipertiroidismo, nódulos de la tiroides y la importancia de la enfermedad de la tiroides durante el embarazo, b) la enfermedad adrenal en la hipertensión y el enfoque de la incidentaloma suprarrenal c) hiperparatiroidismo primario y la deficiencia de vitamina D d) Trastornos gonadal y la importancia de la detección precoz de la enfermedad hormonal, tanto en la disfunción ovárica y testicular

We review the most common disorders of the endocrine system that are detected in non-specialist consultation. Emphasis is placed on: a) thyroid disorders such as hypo-or hyperthyroidism, thyroid nodules and the importance of thyroid disease during pregnancy, b) adrenal disease in hypertension and the approach to the adrenal incidentaloma c) metabolic disorders such as primary hyperparathyroidism and vitamin Ddeficiency d) gonadal disorders and the importance of early detection of hormonal disease in both ovarian and testicular dysfunction

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids: [revisão] / Gonadotrophic axis dysfunction in men with HIV-infection/Aids: [review]

A disfunção do eixo gonadotrófico é frequentemente observada em pacientes infectados pelo HIV. A patogênese é multifatorial e está relacionada à duração da infecção pelo HIV, aos efeitos citopáticos diretos do vírus, ao uso de drogas gonadotóxicas, às infecções oportunistas, às neoplasias, à desnutrição, entre outros fatores. Em homens, a redução dos níveis de testosterona está associada à perda de massa e de força muscular, à redução da densidade mineral óssea, à lipodistrofia, à depressão, à astenia, à fadiga e à disfunção sexual. Em pacientes infectados pelo HIV com hipogonadismo, inúmeros estudos têm comprovado os efeitos benéficos da reposição de testosterona sobre o perfil metabólico e a distribuição da gordura corporal, com aumento da massa corporal magra, além de promover melhora da qualidade de vida, reduzir a perda de massa óssea e reduzir os índices de depressão. Assim, esta revisão teve como objetivo trazer uma breve atualização sobre o presente tema, abordando dados epidemiológicos, mecanismos fisiopatológicos e estratégias terapêuticas para as principais anormalidades do eixo gonadotrófico masculino associadas à infecção pelo HIV e ao seu tratamento.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

[Gonadotrophic axis dysfunction in men with HIV-infection/aids]. / Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

Análise clínica e molecular de pacientes com distúrbios do desenvolvimento gonadal / Clinical and molecular analysis of patients with disorders of gonadal development

Introdução: O termo distúrbios do desenvolvimento gonadal (DDG) inclui condições congênitas nas quais o desenvolvimento gonadal é atípico. Estudos feitos em camundongos observaram que alguns genes como o Cbx2 e o Tcf21 interferem na fase inicial do desenvolvimento gonadal, afetando tanto gônadas XX quanto XY. O gene Dhh, por sua vez, codifica o fator de transcrição Dhh, produzido pelas células de Sertoli, que é fundamental para a diferenciação das células de Leydig em gônadas XY. Nos ovários, o gene FOXL2 atua na foliculogênese, sendo fundamental para a formação dos ovários. Objetivos: Analisar clinicamente e pesquisar anormalidades nos genes CBX2, TCF21, DHH e FOXL2 em pacientes portadores de distúrbios do desenvolvimento gonadal 46, XY e 46, XX. Material e Métodos: Foram estudados 60 pacientes (41 com DDG 46, XY e 19 com DDG 46, XX). A análise molecular foi realizada a partir da amplificação gênica por PCR e sequenciamento direto. Resultados: Várias alterações alélicas foram encontradas nos quatro genes, algumas ainda não descritas na literatura. Uma alteração intrônica no gene DHH foi encontrada em um paciente com DDG 46, XY e não foi encontrada em nenhum dos 360 alelos normais estudados (g.IVS2 +29G>A). Estudamos essa variante através da extração do RNA do testículo do paciente afetado, mas não encontramos alteração no RNA; portanto ela parece não ser uma mutação. No gene TCF21, a variante encontrada foi identificada em controles normais. No gene CBX2, das treze alterações encontradas, uma não foi identificada em 206 alelos normais, e há troca de aminoácidos (p.C132R / g.394 T>C). Trata-se de uma variante que pode ter relação com o fenótipo do paciente, portador de DDG 46, XY. No gene FOXL2, das três alterações encontradas, uma não foi identificada em 206 alelos normais; contudo, não há troca de aminoácidos (p.A181A / g.543 C>T). Conclusão: Esse estudo sugere que mutações nos genes CBX2, TCF21, FOXL2 e DHH são causas raras de distúrbios do desenvolvimento...

Introduction: Congenital disorders of gonadal development (DGD) include conditions whose gonadal development is atypical. Studies in mice found that some genes such as Cbx2 and Tcf21 interfere in the initial phase of gonadal development, affecting both XX and XY gonads. Dhh gene, in turn, encodes the transcription factor Dhh, produced by Sertoli cells, which is essential for the differentiation of Leydig cells in XY gonads. In the ovaries, genes as FOXL2 act in folliculogenesis, fundamental to the development of the ovaries. Objectives: To analyze patients with disorders of gonadal development (DGD) 46, XY and 46, XX and research mutations in CBX2, TCF21, DHH and FOXL2 genes. Methods: We analyzed 60 patients (41 DGD 46, XY patients and 19 DGD 46, XX patients). The whole coding region of CBX2, TCF21, DHH and FOXL2 genes were amplified by PCR and direct sequenced. Results: Several allelic variations have been found in the four genes, some not even described by literature. One intronic variation in DHH was described in one patient with 46, XY DGD and it wasnt found in any of the 360 normal control alleles studied (g.IVS2 +29G>A). We studied this variant through RNA extraction from the affected patients testes, but we didnt find any alteration in the RNA, so it doesnt seem to be a mutation. In TCF21 gene, the single variant that was found was identified in normal controls. In CBX2 gene, among the 13 alterations described, one wasnt identified in 206 normal control alleles, and there is aminoacid change (p.C132R / g.394 T>C). This is a variant that may be a mutation, causing the patients phenotype that had 46, XY DGD. In FOXL2, among the 3 variations described, one wasnt indentified in 206 normal control alleles, but there wasnt amino acid change (p.A181A / g.543 C>T).Conclusion: This study suggests that mutations in CBX2, TCF21, FOXL2 and DHH genes are rarely causes of disorders of gonadal development.

Parasitic castration, growth, and sex steroids in the freshwater bonefish Cyphocharax gilbert (Curimatidae) infested by Riggia paranensis (Cymothoidea)

Cyphocharax gilbert shows parasitic castration when infested by the crustacean Riggia paranensis, being unable to reproduce. Fish were sampled in the middle rio Itabapoana, Brazil, to study the prevalence of parasitism, growth, and sex steroid concentrations, considering the body size, sex, and reproductive condition of specimens. Most of the fish analyzed were infested (56.0 percent). The presence of two lines on the scales was more frequent among infested fish (22.0 percent) than among fish without parasites (12.0 percent for females and 10.0 percent for males). The occurrence of three lines on the scales was rare (3.5 percent among infested and 2.0 percent among females without parasites). These results suggest that growth of the host is faster than that of non infested fish. The serum concentrations of sex steroids from fish without parasites varied at different gonadal development stages (17 beta-estradiol: 60.0 to 976.7 pg/ml; total testosterone: 220.0 to 3,887.7 pg/ml). All infested fish had lower levels of the two sex steroids and undeveloped gonads. Sex steroids levels in infested females were close to those in females at post-spawning stages. Total testosterone concentrations of infested males were below those of males at early gonadal maturation stage. These results suggest that R. paranensis reduces the reproductive capacity of C. gilbert by affecting the host endocrine system

Cyphocharax gilbert exibe castração parasitária quando está infestado pelo crustáceo Riggia paranensis, estando impossibilitado de reproduzir. Os peixes foram coletados no trecho médio do rio Itabapoana, Brasil, para analisar a prevalência do parasitismo, quantificar crescimento e as concentrações de esteróides sexuais, considerando o tamanho do corpo, o sexo e a condição reprodutiva dos espécimes. A maioria dos peixes analisados estava infestada (56,0 por cento). A presença de duas linhas em escamas foi mais freqüente entre os peixes infestados (22,0 por cento) que entre os peixes não infestados (12,0 por cento para as fêmeas e 10,0 por cento para os machos). A presença de três linhas na escama foi rara (3,5 por cento entre os peixes infestados e 2,0 por cento entre as fêmeas não infestadas). Estes resultados sugerem que o crescimento no hospeideiro pode ser mais rapido que no peixes não parasitados. As concentrações de esteróides sexuais no soro dos peixes não infestados variaram entre os diferentes estágios reprodutivos (17 beta-estradiol: 60,0 a 976,7 pg/ml; total testosterona: 220,0 a 3.887,7 pg/ml). Todos os peixes infestados apresentaram baixos níveis dos dois hormônios esteroidais e ausência de desenvolvimento gonadal. Os níveis de esteróides sexuais nas fêmeas infestadas foram próximos aos níveis encontrados nas fêmeas pós-desovadas. A concentração de testosterona encontrada nos machos infestados foi inferior àquela obtida nos machos que estavam iniciando o desenvolvimento gonadal. Estes resultados sugerem que R. paranensis impede a reprodução de C. gilbert, afetando o sistema endócrino do hospedeiro

Parasitic castration, growth, and sex steroids in the freshwater bonefish Cyphocharax gilbert (Curimatidae) infested by Riggia paranensis (Cymothoidea)

Cyphocharax gilbert shows parasitic castration when infested by the crustacean Riggia paranensis, being unable to reproduce. Fish were sampled in the middle rio Itabapoana, Brazil, to study the prevalence of parasitism, growth, and sex steroid concentrations, considering the body size, sex, and reproductive condition of specimens. Most of the fish analyzed were infested (56.0 percent). The presence of two lines on the scales was more frequent among infested fish (22.0 percent) than among fish without parasites (12.0 percent for females and 10.0 percent for males). The occurrence of three lines on the scales was rare (3.5 percent among infested and 2.0 percent among females without parasites). These results suggest that growth of the host is faster than that of non infested fish. The serum concentrations of sex steroids from fish without parasites varied at different gonadal development stages (17 beta-estradiol: 60.0 to 976.7 pg/ml; total testosterone: 220.0 to 3,887.7 pg/ml). All infested fish had lower levels of the two sex steroids and undeveloped gonads. Sex steroids levels in infested females were close to those in females at post-spawning stages. Total testosterone concentrations of infested males were below those of males at early gonadal maturation stage. These results suggest that R. paranensis reduces the reproductive capacity of C. gilbert by affecting the host endocrine system(AU)

Cyphocharax gilbert exibe castração parasitária quando está infestado pelo crustáceo Riggia paranensis, estando impossibilitado de reproduzir. Os peixes foram coletados no trecho médio do rio Itabapoana, Brasil, para analisar a prevalência do parasitismo, quantificar crescimento e as concentrações de esteróides sexuais, considerando o tamanho do corpo, o sexo e a condição reprodutiva dos espécimes. A maioria dos peixes analisados estava infestada (56,0 por cento). A presença de duas linhas em escamas foi mais freqüente entre os peixes infestados (22,0 por cento) que entre os peixes não infestados (12,0 por cento para as fêmeas e 10,0 por cento para os machos). A presença de três linhas na escama foi rara (3,5 por cento entre os peixes infestados e 2,0 por cento entre as fêmeas não infestadas). Estes resultados sugerem que o crescimento no hospeideiro pode ser mais rapido que no peixes não parasitados. As concentrações de esteróides sexuais no soro dos peixes não infestados variaram entre os diferentes estágios reprodutivos (17 beta-estradiol: 60,0 a 976,7 pg/ml; total testosterona: 220,0 a 3.887,7 pg/ml). Todos os peixes infestados apresentaram baixos níveis dos dois hormônios esteroidais e ausência de desenvolvimento gonadal. Os níveis de esteróides sexuais nas fêmeas infestadas foram próximos aos níveis encontrados nas fêmeas pós-desovadas. A concentração de testosterona encontrada nos machos infestados foi inferior àquela obtida nos machos que estavam iniciando o desenvolvimento gonadal. Estes resultados sugerem que R. paranensis impede a reprodução de C. gilbert, afetando o sistema endócrino do hospedeiro(AU)

Manifestações endócrinas e metabólicas da Síndrome de Imunodeficiência Adquirida / Endocrine and metabolic manifestations of Acquired Immunodeficiency Syndrome

Os autores revisam os principais distúrbios endócrinos e metabólicos associados à síndrome da imunodeficiência adquirida (Sida/Aids).

In the present paper the endocrine compromising in acquired immunodificiency syndrome (Aids) is reviewed.

Clinical and molecular analysis of human reproductive disorders in Brazilian patients

Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHá, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.

Clinical and molecular analysis of human reproductive disorders in Brazilian patients.

Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHbeta, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.