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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.

Cancer immunotherapy has emerged as a treatment modality, mainly as the result of discoveries in the immune response regulation, including mechanisms that turn off immune responses. Immunogenic cutaneous melanoma is a canonical model for therapeutic immunotherapy studies. "Passive" immunotherapy with monoclonal antibodies (mAbs) has outpaced "active" immunotherapy with anti-tumor vaccines, and mAbs that antagonize the off responses have been recently introduced in clinical practice. Despite these recent successes, many unresolved practical and theoretical questions remain. Notably unknown are the identity of the lymphocytes that eliminate tumor cells, which white cells enter into tumors, through which endothelium, in what order, and how they perform their task. The parameters of size and location that could be used to determine in which tumors the immune response may be sufficient to eradicate the tumor are yet unknown. Immunotherapy has been so far more efficient to treat solid and hematologic tumors located outside the central nervous system, than primary brain tumors and brain metastases. In contrast to recent advances with mAbs, anti-tumor vaccine development has been lagging behind. The multiplicity of antigens that must be targeted to achieve significant clinical response is partially responsible for this lag, especially in melanoma, one of the most mutated tumors. Further hampering vaccination results is the fact that tumor elimination by the immune system is the result of a race between tumors with different growth rates and the relatively slow development of the adaptive immune response. The enhancement of the native arm of the immune response or the administration of targeted chemotherapy to slow tumor development, are approaches that should be studied. Finally, criteria used to analyze patient response to immunotherapeutic treatments must be perfected, and the patient populations that could benefit the most from this approach must be better defined.