Testicular expression of the TGF-B1 system and the control of Leydig cell proliferation

Transforming growth factor beta 1 (TGF-beta1) is a key regulator that modulates male reproductive function. Testicular TGF-beta1 modulates the steroidogenesis of Leydig cells, the organization of peritubular myoid cells, testis development and spermatogenesis. Several studies have indicated that TGF-beta1 is involved in the tight balance between proliferative and apoptotic re- sponses in the Leydig cells. In the present review, we summarize the direct effects of this cytokine in Ley- dig cells under normal and pathological conditions. We analyze the effect of TGF-beta1 in Leydig cells de- pending on the type of receptors involved in the sig- naling pathway of TGF-beta1. Our group has been ana- lyzing the canonical and non canonical intracellular signaling pathways of TGF-beta1 that are involved in the expression of proliferative and apoptotic markers in Leydig cells. On the basis of our studies and from those of other authors we conclude that the balance between the expression of TGF-beta1 receptors and co receptors is of relevance in Leydig cell physiology and pathophisiology.Fil: Gonzalez, Candela Rocio. Universidad Maimonides. Area de Invest.biomedicas y Biotecnologicas; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Gonzalez Calvar, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Cyclooxygenase and prostaglandins in somatic cell populations of the testis

rostaglandins (PGs) are synthesized through the action of the rate-limiting enzyme cyclooxygenase (COX) and further specific enzymes. The development of Cox-deficient mice in the 1990s gave insights into the reproductive roles of PGs. Female Cox-knockout mice were subfertile or infertile. Interestingly, fertility was not affected in male mice deficient in Cox, suggesting that PGs may not be critical for the functioning of the testis. However, this conclusion has recently been challenged by observations of important roles for PGs in both physiological and pathological processes in the testis. The two key somatic cell types in the testis, Leydig and Sertoli cells, express the inducible isoenzyme COX2 and produce PGs. Testicular COX2 expression in these somatic cells is regulated by hormonal input (FSH, prolactin (PRL), and testosterone) as well as by IL1β. PGs modulate steroidogenesis in Leydig cells and glucose uptake in Sertoli cells. Hence, the COX2/PG system in Leydig and Sertoli cells acts as a local modulator of testicular activity, and consequently may regulate spermatogenic efficiency. In addition to its expression in Leydig and Sertoli cells, COX2 has been detected in the seminiferous tubule wall, and in testicular macrophages and mast cells of infertile patients. These observations highlight the possible relevance of PGs in testicular inflammation associated with idiopathic infertility. Collectively, these data indicate that the COX2/PG system plays crucial roles not only in testicular physiology (i.e., development, steroidogenesis, and spermatogenesis), but more importantly in the pathogenesis or maintenance of infertility status in the male gonad. Further studies of these actions could lead to new therapeutic approaches to idiopathic male infertility.Fil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mayerhofer, Artur. Zellbiologie Universität München; AlemaniaFil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentin

Peripheral and central mechanisms involved in hormonal control of male and female reproduction

Reproduction involves the integration of hormonal signals acting across multiple systems togenerate a synchronized physiological output. A critical component of reproduction is the luteinizinghormone (LH) surge, which is mediated by estradiol (E2) and neuroprogesterone interacting tostimulate kisspeptin release in the rostral periventricular nucleus of the third ventricle in rats. Recentevidence has shown that both classical and membrane E2 and progesterone signaling is involved inthis pathway. A metabolite of gonadotropin-releasing hormone (GnRH), GnRH-(1-5), has been shownto stimulate GnRH expression, secretion, and has a role in the regulation of lordosis. Additionally,gonadotropin-inhibitory hormone (GnIH) projects to and influences the activity of GnRH neurons inbirds. Stress-induced changes in GnIH have been shown to alter breeding behaviors in birds,demonstrating another molecular control of reproduction. Peripherally, paracrine and autocrineactions within the gonad have been suggested as therapeutic targets for infertility in both males andfemales. Dysfunction of testicular prostaglandin synthesis is a possible cause of idiopathic maleinfertility. Indeed, local production of melatonin and corticotropin-releasing hormone (CRH) couldinfluence spermatogenesis via immune pathways in the gonad. In females, vascular endothelialgrowth factor A (VEGF-A) has been implicated in an angiogenic process that mediates developmentof the corpus luteum and thus fertility via the Notch signaling pathway. Age-induced decreases infertility involve ovarian kisspeptin and its regulation of ovarian sympathetic innervation. Finally,morphological changes in the arcuate nucleus of the hypothalamus influence female sexualreceptivity in rats. The processes mediating these morphological changes have been shown toinvolve rapid effects of E2 controlling synaptogenesis in this hypothalamic nucleus. Together, thisreview highlights new research in these areas, focusing on recent findings in the molecularmechanisms of central and peripheral hormonal control of reproduction.Fil: Rudolph, L. M.. University of California at Los Angeles; Estados UnidosFil: Bentley, G. E.. University of California Berkeley; Estados UnidosFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Paredes, A. H.. Universidad de Chile; ChileFil: Tesone, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Wu, T. J.. Uniformed Services University; Estados UnidosFil: Micevych, P. E.. University of California at Los Angeles; Estados Unido

The influence of cabergoline on the offspring phenotype of human chorionic gonadotropin (hCG)- secreting female mice: does mother's milk make the difference?

Transgenic female mice expressing human chorionic gonadotropin-ß (hCGß +) produce elevated levels of hCG, prolactin and progesterone, show precocious puberty, are infertile and develop pituitary tumors. We have previously demonstrated that a short-term treatment of juvenile hCGß + females with the dopamine agonist cabergoline normalizes the phenotypic changes of hCGß + females. Even more, the treatment prevented phenotypic alterations on the transgenic offspring. The aim of this study was to determine if the cabergoline treatment has its effect during pregnancy and/or lactation. Two groups of 2-month-old wild-type (WT) females were mated with hCGß + males: (1) Six-week-old WT females pretreated with cabergoline (500 µ g/kg, ip), every other day for one week (WT-CAB mothers); (2) WT females without treatment (WT- mothers).Fil: Marcial López, Carla Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaInternational Symposium on Reproductive Health: overcoming barriers for research in reproductionBuenos AiresArgentinaISRH2021 1 Scientific and Organizing CommitteeCEFYBO-CONICETUniversidad de Buenos Aires. Facultad de Medicin

Hormonal Regulation of Follicle-Stimulating Hormone Glycosylation in Males

The Follicle-Stimulating Hormone plays an important role in the regulation of gametogenesis. It is synthesized and secreted as a family of glycoforms with differing oligosaccharide structure, biological action, and half-life. The presence of these oligosaccharides is absolutely necessary for the full expression of hormone bioactivity at the level of the target cell. The endocrine milieu modulates the glycosylation of this hormone. During male sexual development a progressive increase in FSH sialylation and in the proportion of glycoforms bearing complex oligosaccharides are the main features in this physiological condition. In late puberty, FSH oligosaccharides are largely processed in the medial- and trans-Golgi cisternae of the gonadotrope and remain without changes throughout adult life. In experimental models, the absence of gonads severely affects FSH sialylation; androgen administration is able to restore the characteristics observed under physiological conditions. The expression of ST6 beta-galactoside alpha-2,6-sialyltransferase 1 is hormonally regulated in the male rat; it decreases after short periods of castration but increases markedly at longer periods of androgen deprivation. Although ST3 beta-galactoside alpha-2,3-sialyltransferase 3 is expressed in the male rat pituitary it is not influenced by changes in the endocrine milieu. The oligosaccharide structure of FSH has an impact on the Sertoli cell endocrine activity. In more advanced stages of Sertoli cell maturation, both sialylation and complexity of the oligosaccharides are involved in the regulation of inhibin B production; moreover, FSH glycoforms bearing incomplete oligosaccharides may enhance the stimulatory effect exerted by gonadal growth factors. In this review, we discuss available information on variation of FSH glycosylation and its hormonal regulation under different physiological and experimental conditions, as well as the effect on Sertoli cell endocrine activity.The Follicle-Stimulating Hormone plays an important role in the regulation of gametogenesis. It is synthesized and secreted as a family of glycoforms with differing oligosaccharide structure, biological action, and half-life. The presence of these oligosaccharides is absolutely necessary for the full expression of hormone bioactivity at the level of the target cell. The endocrine milieu modulates the glycosylation of this hormone. During male sexual development a progressive increase in FSH sialylation and in the proportion of glycoforms bearing complex oligosaccharides are the main features in this physiological condition. In late puberty, FSH oligosaccharides are largely processed in the medial- and trans-Golgi cisternae of the gonadotrope and remain without changes throughout adult life. In experimental models, the absence of gonads severely affects FSH sialylation; androgen administration is able to restore the characteristics observed under physiological conditions. The expression of ST6 beta-galactoside alpha-2,6-sialyltransferase 1 is hormonally regulated in the male rat; it decreases after short periods of castration but increases markedly at longer periods of androgen deprivation. Although ST3 beta-galactoside alpha-2,3-sialyltransferase 3 is expressed in the male rat pituitary it is not influenced by changes in the endocrine milieu. The oligosaccharide structure of FSH has an impact on the Sertoli cell endocrine activity. In more advanced stages of Sertoli cell maturation, both sialylation and complexity of the oligosaccharides are involved in the regulation of inhibin B production; moreover, FSH glycoforms bearing incomplete oligosaccharides may enhance the stimulatory effect exerted by gonadal growth factors. In this review, we discuss available information on variation of FSH glycosylation and its hormonal regulation under different physiological and experimental conditions, as well as the effect on Sertoli cell endocrine activity.Fil: Campo, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Campo, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Ambao, Veronica Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Ambao, Veronica Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Urrutia, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Urrutia, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Alterations in oxidative, inflammatory and apoptotic events in short-lived and long-lived mice testes

Aged testes undergo profound histological and morphological alterations leading to a reduced functionality. Here, we investigated whether variations in longevity affect the development of local inflammatory processes, the oxidative state and the occurrence of apoptotic events in the testis. To this aim, well-established mouse models with delayed (growth hormone releasing hormone-knockout and Ames dwarf mice) or accelerated (growth hormone-transgenic mice) aging were used. We hereby show that the testes of short-lived mice show a significant increase in cyclooxygenase 2 expression, PGD2 production, lipid peroxidation, antioxidant enzymes expression, local macrophages and TUNEL-positive germ cells numbers, and the levels of both pro-caspase-3 and cleaved caspase-3. In contrast, although the expression of antioxidant enzymes remained unchanged in testes of long-lived mice, the remainder of the parameters assessed showed a significant reduction. This study provides novel evidence that longevity confers anti-inflammatory, anti-oxidant and anti-apoptotic capacities to the adult testis. Oppositely, short-lived mice suffer testicular inflammatory, oxidative and apoptotic processes.Fil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Miquet, Johanna Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fang, Yimin. Southern Illinois University. School Of Medicine; Estados UnidosFil: Hill, Cristal Monique. Southern Illinois University; Estados UnidosFil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bartke, Andrzej. Southern Illinois University; Estados UnidosFil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentin

Hallmarks of testicular aging: the challenge of anti-inflammatory and antioxidant therapies using natural and/or pharmacological compounds to improve the physiopathological status of the aged male gonad

The evolutionary theory of aging supports a trade-off relationship between reproduction and aging. Aging of the male reproductive system primarily affects the testes, leading to a decrease in the levels of sexual hormones, alterations in sperm quality and production, and a decline in fertility that does not necessarily involve a complete cessation of spermatogenesis. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases that are frequently observed in aged testes. Although the molecular mechanisms are still poorly understood, accumulating evidence points toward pro-inflammatory molecules and reactive oxygen species as primary contributing factors for testicular aging. However, the real impact of aging-related testicular alterations on fertility, reproductive health, and life span is far from being fully revealed. This work discusses the current knowledge on the impact of aging in the testis, particularly of aging-related dysregulated inflammation and oxidative damage on the functioning of its different cell populations. More interestingly, this review covers the potential benefits of anti-aging interventions and therapies using either pharmacological compounds (such as non-selective non-steroidal anti-inflammatory medication) or more natural alternatives (such as various nutraceuticals or even probiotics) that exhibit anti-inflammatory, antioxidant, and anti-apoptotic properties. Some of these are currently being investigated or are already in clinical use to delay or prevent testicular aging.Fil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Bartke, Andrzej. Southern Illinois University; Estados UnidosFil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Ciclo Básico Común; Argentin

Hyperprolactinemia induced by hCG leads to metabolic disturbances in female mice

The metabolic syndrome is a growing epidemic; it increases the risk for diabetes, cardiovascular disease, fatty liver, and several cancers. Several reports have indicated a link between hormonal imbalances and insulin resistance or obesity. Transgenic (TG) female mice overexpressing the human chorionic gonadotropin β-subunit (hCGβ+ mice) exhibit constitutively elevated levels of hCG, increased production of testosterone, progesterone and prolactin, and obesity. The objective of this study was to investigate the influence of hCG hypersecretion on possible alterations in the glucose and lipid metabolism of adult TG females. We evaluated fasting serum insulin, glucose, and triglyceride levels in adult hCGβ+ females and conducted intraperitoneal glucose and insulin tolerance tests at different ages. TG female mice showed hyperinsulinemia, hypertriglyceridemia, and dyslipidemia, as well as glucose intolerance and insulin resistance at 6 months of age. A 1-week treatment with the dopamine agonist cabergoline applied on 5-week-old hCGβ+ mice, which corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, effectively prevented the metabolic alterations. These data indicate a key role of the hyperprolactinemia-induced gonadal dysfunction in the metabolic disturbances of hCGβ+ female mice. The findings prompt further studies on the involvement of gonadotropins and prolactin on metabolic disorders and might pave the way for the development of new therapeutic strategies.Fil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Stevens, Guillermina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bonaventura, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Poutanen, Matti. University of Turku; FinlandiaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Huhtaniemi, Ilpo T.. University of Turku; FinlandiaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

A Ca2+-activated potassium channel (BKCa) in Leydig cells is involved in testosterone production

Previously, we found that human steroid-producing ovarian granulosa cells express all major types of Ca2+-activated potassium channels (KCa), including BKCa, IK and SKs (Traut et al., RB&E, 2009), and that modulation of the activity of these channels resulted in alteration of steroid production. In the male gonad Leydig cells produce androgens, but whether these cells are endowed with KCas is not known. We addressed these points and focussed on BKCa, which is Ca2+-activated and the underlying channel for a prominent current. It can be manipulated, e.g. by a specific blocker, the red scorpion toxin iberiotoxin (IbTx), which binds to the outer face with high affinity and selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.Fil: Siebert, S. Ludwig Maximilians Universität München. ; AlemaniaFil: Spinnler, K. Ludwig Maximilians Universität München. ; AlemaniaFil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kunz, L. Ludwig Maximilians Universität München. ; AlemaniaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mayerhofer, A. Ludwig Maximilians Universität München. ; Alemania22. Jahrestagung der Deutschen Gesellschaft für Andrologie e VHamburgoAlemaniaDeutsche Gesellschaft für AndrologieConventus Congressmanagement und Marketing Gmb

Efeitos gonadais e extra-gonadais da hipersecreção do hormônio gonadotrofina coriônica humana: avaliação num modelo de camundongos transgênicos

Nuestro grupo de investigación está enfocado en estudiar los efectos gonadales y extra-gonadales que ejerce la hormona gonadotrofina coriónica humana (hCG) sobre la función endocrina y reproductiva, particularmente en condiciones de secreción desregulada y persistente. La tecnología transgénica ha resultado ser una herramienta fundamental a la hora de proveer nuevas evidencias sobre el rol de las gonadotrofinas en la patofisiología reproductiva. En este sentido, los ratones transgénicos hipersecretores de hCG han resultado un excelente modelo para llevar a cabo dichas investigaciones. Hemos realizado estudios de caracterización del modelo, que nos ha permitido tener un profundo conocimiento del mismo e identificar un gran número de anomalías en distintos niveles de regulación endocrina, que serán el foco de atención en futuras investigaciones. Las mismas tienen un considerable potencial en el campo de la biomedicina, ya que ayudarán a identificar los mecanismos regulatorios afectados por un estímulo disruptivo como puede ser una hipersecreción hormonal, y permitirán la exploración de nuevas estrategias terapéuticas que interfieran en las patologías endocrinas asociadas. Nuestras investigaciones sobre el modelo de hipersecreción crónica de hCG en ratones muestran claramente que niveles elevados y persistentes de esta hormona promueven múltiples anomalías endocrinas que están acompañadas de tumores gonadales y extra-gonadales.This investigation is focused in studying the gonadal and extra-gonadal effects that the human chorionic gonadotropin hormone (hCG) exerts on endocrine and reproductive functions, particularly under deregulated and persistent secretion conditions. Transgenic technology has turned out to be a fundamental tool when providing new evidences on the role of gonadotropins in reproductive physiopathology. In this sense, transgenic mice hCG hypersecretion has been an excellent model to perform these investigations. Characterization studies of the model have been developed to identify a great number of anomalies in different levels of endocrine regulation, which will be the center of attention in subsequent investigations. These have a considerable potential in the field of biomedicine and will help to identify the regulatory mechanisms affected by a disruptive stimulus, such as hormonal hypersecretion, and will enable the exploration of new therapeutic strategies to interfere with endocrine pathologies. Our investigations on the model of chronic hypersecretion of hCG in mice show clearly that high and persistent levels of this hormone promote manifold endocrine anomalies that are accompanied by gonadal and extra-gonadal tumorsNosso grupo de pesquisa está focado em estudar os efeitos gonadais e extra-gonadais que exerce o hormônio gonadotrofina coriônica humana (hCG) sobre a função endócrina e reprodutiva, particularmente em condições de secreção desregulada e persistente. A tecnologia transgênica tem resultado ser uma ferramenta fundamental na hora de fornecer novas evidências sobre o papel das gonadotrofinas na patofisiologia reprodutiva. Nesse sentido, os camundongos transgênicos hipersecretores de hCG têm resultado um excelente modelo para levar a cabo tais pesquisas. Temos realizado estudos de caracterização do modelo, que nos têm permitido ter um profundo conhecimento do mesmo e identificar um grande número de anomalias em diferentes níveis de regulação endócrina, que serão o foco de atenção em futuras pesquisas. As mesmas têm um considerável potencial no campo da biomedicina, visto que ajudarão a identificar os mecanismos regulatórios afetados por um estímulo disruptivo como pode ser uma hipersecreção hormonal, e permitirão a exploração de novas estratégias terapêuticas que interfiram nas patologias endócrinas associadas. Nossas pesquisas sobre o modelo de hipersecreção crônica de hCG em camundongos mostram claramente que níveis elevados e persistentes deste hormônio promovem múltiplas anomalias endócrinas que estão acompanhadas de tumores gonadais e extra-gonadais.Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Stevens, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin