5 research outputs found
Regulaci贸n hormonal del grado de sializaci贸n de la FSH y su posible implicancia fisiol贸gica
FSH is produced and secreted as a family of glycosylation variants which differ from\neach other in the sialylation and complexity degree of its oligosaccharides and in the\ninduction of biological responses. El objetivo general de esta Tesis Doctoral fue\ndeterminar la regulaci贸n hormonal y el mecanismo por el cual se producen cambios en\nel grado de sializaci贸n de la mol茅cula de FSH y su posible implicancia sobre la\nregulaci贸n de la funci贸n testicular.\nThe aim of this Doctoral Thesis was to determine the mechanisms involved in the\nhormonal regulation of FSH sialylation and the impact of this characteristic on the\ntesticular function. Alterations in serum FSH sialylation, in GnRH and in androgen\nactions were observed in anorquid patients. An increment in FSH sialylation was\nobserved during sexual development in the rat. Castration, androgens and GnRH\nantagonist affected FSH glycosylation and the gene expression of St6gal1. Different\ncharge analogues isolated from FSHrh induced differential responses on the estradiol,\ncAMP and inhibins production by immature Sertoli cells.\nThese results show that the regulation of sialyltransferases gene expression, FSH\nsialylation degree ? involved in the differential response of the target cell ? require the\nfunctional integrity of the hypothalamic?pituitary?testicular axis.Fil: Ambao, Ver贸nica Ana. Universidad de Buenos Aires. Facultad de Farmacia y Bioqu铆mica. Buenos Aires, ArgentinaLa FSH se sintetiza y secreta como una familia de variantes glicosiladas, las cuales\ndifieren en el grado de sializaci贸n y complejidad de sus oligosac谩ridos y en la inducci贸n\nde respuestas biol贸gicas en c茅lulas blanco. El objetivo general de esta Tesis Doctoral fue\ndeterminar la regulaci贸n hormonal y el mecanismo por el cual se producen cambios en\nel grado de sializaci贸n de la mol茅cula de FSH y su posible implicancia sobre la regulaci贸n\nde la funci贸n testicular. En pacientes an贸rquidos se observaron alteraciones en el grado\nde sializaci贸n de la FSH s茅rica, en la acci贸n del GnRH y andr贸genos. El grado de\nsializaci贸n de FSH se increment贸 durante el desarrollo sexual de la rata. La castraci贸n,\nlos andr贸genos y un antagonista de GnRH afectaron la glicosilacion de la FSH hipofisaria\ny la expresi贸n g茅nica de la St6gal1. Variantes glicosiladas de FSHrh indujeron respuestas\ndiferenciales en la producci贸n de estradiol, AMPc e inhibinas en c茅lulas de Sertoli\ninmaduras. Los resultados obtenidos demuestran que la regulaci贸n de la expresi贸n\ng茅nica de sialiltransferasas, del grado de sializaci贸n de la FSH ? involucrado en la\nrespuesta diferencial de la c茅lula blanco ? requiere de la integridad funcional del eje\nhipot谩lamo?hip贸fiso?testicular
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
Role of FSH glycan structure in the regulation of Sertoli cell inhibin production
Variations in follicle-stimulating hormone (FSH) carbohydrate composition and structure are associated with important structural and functional changes in Sertoli cells (SCs) during sexual maturation. The aim of the present study was to investigate the impact of FSH oligosaccharide structure and its interaction with gonadal factors on the regulation of monomeric and dimeric inhibin production at different maturation stages of the SC. Recombinant human FSH (rhFSH) glycosylation variants were isolated according to their sialylation degree (AC and BA) and complexity of oligosaccharides (CO and HY). Native rhFSH stimulated inhibin 伪-subunit (Pro-伪C) but did not show any effect on inhibin B (INHB) production in immature SCs isolated from 8-day-old rats. Activin A stimulated INHB and had a synergistic effect on FSH to stimulate Pro-伪C. The less acidic/sialylated rhFSH charge analogues, BA, were the only charge analogue mix that stimulated INHB as well as the most potent stimulus for Pro-伪C production. Native rhFSH stimulated both Pro-伪C and INHB in SCs at a more advanced maturation stage, isolated from 20-day-old rats. In these cells, all rhFSH glycosylation variants increased INHB and Pro-伪C production, even in the presence of growth factors. The BA preparation exerted a more marked stimulatory effect on INHB and Pro-伪C than the AC. Glycoforms bearing high mannose and hybrid-type oligosaccharides, HY, stimulated INHB and Pro-伪C more effectively than those bearing complex oligosaccharides, CO, even in the presence of gonadal growth factors. These findings demonstrate the modulatory effect of FSH oligosaccharide structure on the regulation of inhibin production in the male gonad.Fil: Andreone, Luz. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Parque Centenario. Instituto de Investigaci贸n en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Ambao, Veronica Ana. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Parque Centenario. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Fundaci贸n de Endocrinolog铆a Infantil. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada"; ArgentinaFil: Pellizzari, Eliana Herminia. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Parque Centenario. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Fundaci贸n de Endocrinolog铆a Infantil. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada"; ArgentinaFil: Loreti, Rosana Nazareth. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Parque Centenario. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Fundaci贸n de Endocrinolog铆a Infantil. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada"; ArgentinaFil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Parque Centenario. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Fundaci贸n de Endocrinolog铆a Infantil. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada"; ArgentinaFil: Campo, Stella Maris. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Oficina de Coordinaci贸n Administrativa Parque Centenario. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada". Fundaci贸n de Endocrinolog铆a Infantil. Centro de Investigaciones Endocrinol贸gicas "Dr. C茅sar Bergada"; Argentin
Usefulness of the Anti-Mullerian Hormone (AMH) and Inhibin B in the diagnosis of Hypogonadism in the child
Durante la infancia, el eje hipot谩lamo-hip贸fiso-testicular se encuentra parcialmente quiescente: bajan los niveles
de gonadotrofinas y la secreci贸n de testosterona disminuye siguiendo a la ca铆da de la LH. Por el contrario, las
c茅lulas de Sertoli est谩n activas, como lo demuestran los niveles s茅ricos de hormona anti-m眉lleriana (AMH) e
inhibina B. Por lo tanto, el hipogonadismo en la infancia puede ser puesto en evidencia, sin necesidad de pruebas
de est铆mulo, si se eval煤a la funci贸n de las c茅lulas de Sertoli. La AMH s茅rica es alta desde la vida fetal hasta el inicio
de la pubertad. La producci贸n testicular de AMH aumenta en respuesta a la FSH pero es potentemente inhibida
por los andr贸genos. La inhibina B es alta en los primeros a帽os de la vida, luego disminuye parcialmente aunque
permanece claramente m谩s alta que en las mujeres, y aumenta nuevamente en la pubertad. Las concentraciones
s茅ricas de AMH e inhibina B son indetectables en pacientes an贸rquidos. En el hipogonadismo primario que
afecta a todo el test铆culo, establecido durante la vida fetal o la infancia, todos los marcadores testiculares est谩n
bajos. Cuando en el hipogonadismo est谩n afectadas s贸lo las c茅lulas de Leydig, la AMH y la inhibina B s茅rica son
normales y/o altas, mientras que est谩n bajas cuando se ven afectadas las c茅lulas de Sertoli. La AMH y la inhibina
B est谩n bajas en varones con hipogonadismo central en edad prepuberal y contin煤an bajas en edad puberal. El tratamiento con FSH induce un aumento en los niveles s茅ricos de los marcadores de la c茅lula de Sertoli. En
conclusi贸n, la determinaci贸n de los niveles s茅ricos de AMH e inhibina B es 煤til para evaluar la funci贸n testicular, sin
necesidad de pruebas de est铆mulo, y orientar el diagn贸stico etiol贸gico en el hipogonadismo masculino en pediatr铆[email protected] childhood, the hypothalamic-pituitary-gonadal axis is partially quiescent: gonadotropin and testosterone
levels decrease, but Sertoli cells remain active, as shown by serum anti-M眉llerian hormone (AMH) and inhibin
B levels. Therefore, hypogonadism may be diagnosed during childhood, without the need for stimulation tests,
provided Sertoli cell function is assessed. Serum AMH levels are high from fetal life until the onset of puberty.
Testicular AMH production increases in response to FSH but is potently inhibited by androgens. Serum inhibin
B levels are high until the age of 3-4 years in boys; although they decrease thereafter, they remain clearly
higher than in girls of the same age. During the early stage of puberty, serum inhibin B increases again to
reach adult values. AMH and inhibin B are undetectable in the serum of anorchid patients. In boys with fetalonset
primary hypogonadism affecting the whole testicular parenchyma, AMH and inhibin B are low in serum.
Conversely, they are normal or high when only the interstitial tissue of the gonads is impaired. AMH and inhibin
B are low in children with central hypogonadism and persist low during pubertal age. FSH treatment induces
an increase in both Sertoli cell markers. In conclusion, the determination of serum AMH and inhibin B levels is useful for the assessment of testicular function, without the need for stimulation tests, in pediatric patients