Extragonadal LH/hCG action-Not yet time to rewrite textbooks

Gonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well-established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG. Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.Fil: Pakarainen, Tomi. University of Turku; FinlandiaFil: Ahtiainen, Petteri. University of Turku; FinlandiaFil: Zhang, Fu Ping. University of Helsinki; 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; ArgentinaFil: Poutanen, Matti. University of Turku; FinlandiaFil: Huhtaniemi, Ilpo. University of Turku; Finlandia. IMperial College London; Reino Unid

Sex differences in the pituitary TGFβ1 system: the role of TGFβ1 in prolactinoma development

Prolactinomas are the most frequent functioning pituitary adenomas, and sex differences in tumor size, behavior and incidence have been described. These differences have been associated with earlier diagnosis in woman, as well as with serum estradiol levels. Experimental models of prolactinomas in rodents also show a higher incidence in females, and recent findings suggest that gender differences in the transforming growth factor beta 1 (TGFbeta1) system might be involved in the sex-specific development of prolactinomas in these models. The aim of this review is to summarize the literature supporting the important role of TGFbeta1 as a local modulator of pituitary lactotroph function and to provide recent evidencefor TGF1 involvement in the sex differences found in prolactinoma development in animal models.Fil: Recouvreux, Maria Victoria. 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. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Faraoni, Erika Yanil. 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: Camilletti, María Andrea. 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: Abeledo Machado, Alejandra Inés. 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: Diaz, Graciela Susana. 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

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

Mouse models of altered gonadotrophin action: insight into male reproductive disorders

The advent of technologies to genetically manipulate the mouse genome has revolutionised research approaches, providing a unique platform to study the causality of reproductive disorders in vivo. With the relative ease of generating genetically modified (GM) mouse models, the last two decades have yielded multiple loss-of-function and gain-of-function mutation mouse models to explore the role of gonadotrophins and their receptors in reproductive pathologies. This work has provided key insights into the molecular mechanisms underlying reproductive disorders with altered gonadotrophin action, revealing the fundamental roles of these pituitary hormones and their receptors in the hypothalamic–pituitary–gonadal axis. This review will describe GM mouse models of gonadotrophins and their receptors with enhanced or diminished actions, specifically focusing on the male. We will discuss the mechanistic insights gained from these models into male reproductive disorders, and the relationship and understanding provided into male human reproductive disorders originating from altered gonadotrophin action.Fil: Jonas, Kim C.. Imperial College London; Reino UnidoFil: Oduwole, Olayiwola O.. Imperial College London; Reino UnidoFil: Peltoketo, Hellevi . University of Oulu; FinlandiaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Huhtaniemi, Ilpo T. . Imperial College London; Reino Unido. University of Turku; Finlandi

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

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

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

Making of a unique birth control vaccine against hCG with additional potential of therapy of advanced stage cancers and prevention of obesity and insulin resistance

Reviewed is the work which led to the development of a unique vaccine that prevents pregnancy in sexually active women without impairment of ovulation and block of their making normally their sex steroid hormones. Being given that hCG is not expressed by non-pregnant females, immunization with the vaccine is devoid of any crossreaction with any tissue of the body. It is totally reversible and women regained fertility on decline of antibodies. A recombinant vaccine has been developed which is highly immunogenic in mice. It is undergoing extensive toxicology under GLP conditions in rodents and a primate species, the marmosets, before resumption of clinical trials. Ectopic expression of hCG or its subunits takes place in a variety of cancers, particularly at advanced stage with adverse survival and poor prognosis. Anti-hCG antibodies exercise therapeutic action against such cancers as indicated by in vitro culture and in vivo studies in nude mice. Transgenic hCG β mice put on weight and manifest insulin resistance. Immunization of these mice with the recombinant hCG β-LTB vaccine prevents obesity and insulin resistance.Fil: Talwar, G. P.. Talwar Research Foundation; IndiaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Vyas, Hemant. Harvard Medical School; Estados UnidosFil: Purswani, Shilpi. Talwar Research Foundation; IndiaFil: Kabeer, Rafi Shiraz. Talwar Research Foundation; IndiaFil: Chopra, Prem. Sir Ganga Ram Hospital; IndiaFil: Singh, Priyanka . Talwar Research Foundation; IndiaFil: Atrey, Nishu. Talwar Research Foundation; IndiaFil: Nand, Kripa. Talwar Research Foundation; IndiaFil: Gupta, Jagdish C.. Talwar Research Foundation; Indi

Regulation of the hypothalamic-pituitary-gonadal axis in the male rat : role of androgens

El desarrollo sexual en la rata macho es un proceso complejo que involucra interacciones entre el hipotálamo, hipófisis, testículo y órganos sexuales accesorios. El propósito de esta Tesis ha sido estudiar la influencia de los andrógenos sobre distintos aspectos de la regulación del eje hipotálamo-hipófiso-gonadal en la rata macho, resaltando la importancia de estos eventos durante el desarrollo sexual. Se evaluaron las posibles alteraciones en el perfil hormonal en suero en la rata macho prepúber, originadas por el bloqueo de la acción androgénica a través de la administración de los antiandrógenos flutamida y casodex. Se analizó también el efecto de estos antiandrógenos sobre la función testicular y el trofismo epididimario. Se caracterizaron las distintas isoformas de FSH hipofisaria en la rata macho, de acuerdo a la estructura interna de los oligosacáridos unidos al polipéptído, mediante la separación de las mismas por cromatografía en concanavalina A. Se estudió la influencia de la edad y del entorno androgénico sobre la heterogeneidad de FSH, en términos de inmuno y bioactividad. Estos resultados contribuyen al conocimiento de los mecanismos de regulación de los andrógenos sobre el eje reproductivo en la rata macho, los cuales se manifiestan a través de una amplia diversidad de efectos sobre los distintos niveles que conforman el eje

What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?

The two gonadotrophins, follicle-stimulating hormone and luteinising hormone, are pivotal regulators of the development and maintenance of normal fertility by maintaining testicular and ovarian endocrine function and gametogenesis. Too low gonadotrophin secretion, i.e. hypogonadotrophic hypogonadism, is a common cause of infertility. But there are also physiological and pathophysiological conditions where gonadotrophin secretion and/or action are either transiently or chronically elevated, such as pregnancy, pituitary tumours, polycystic ovarian syndrome, activating gonadotrophin receptor mutations, perimenopause and menopause. These situations can be either the primary or secondary cause of infertility and gonadal pathologies in both sexes. Also the role of gonadotrophins as tumour promoters is possible. Recently, the possibility to combine information from genetically modified mice and human phenotypes in connection with mutations of gonadotrophin or gonadotrophin receptor genes has elucidated many less well known mechanisms involved in dysregulation of gonadotrophin function. Among the genetically modified mouse models, transgenic mice with gonadotrophin hypersecretion have been developed during the last few years. In this review, we describe the key findings on transgenic mouse models overexpressing gonadotrophins and present their possible implications in related human pathologies. In addition, we provide examples of genetic mouse models with secondary effects on gonadotrophin production and, consequently, on gonadal function.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: Huhtaniemi, Ilpo. Imperial College London; Reino Unid