Relevance of components of the hypothalamic–pituitary–gonadal axis in the pathophysiology of nervous system proteinopathies

Abstract

Introduction: Several proteinopathies of the nervous system are associated with disturbances in components of the hypothalamic–pituitary–gonadal axis.Objective: To assess the relevance of components of the hypothalamic–pituitary–gonadal axis to the pathophysiology of nervous system proteinopathies.Material and Methods: A literature review was carried out from January to December 2018. Several databases were searched by using Boolean operators. The advanced search strategy was used for the selection of articles, and the methodological quality and validity of the studies were taken into account.Results: Disturbances of the normal function of the hypothalamic–pituitary–gonadal axis were identified in several nervous system proteinopathies. The most frequently reported disturbances were the increase in gonadotropins levels, mainly in luteinizing hormone, in Alzheimer´s disease, and the decrease in testosterone levels in Alzheimer´s, Parkinson´s and Huntington´s diseases, and Amyotrophic Lateral Sclerosis, with the resulting worsening of the clinical phenotype. Preliminary evidence was obtained pointing to a possible hypothalamic dysfunction in Spinocerebellar ataxia patients.Conclusions: Even when evidence were gathered supporting a link between the pathophysiology of nervous system proteinopathies and disturbances in components of the hypothalamic–pituitary–gonadal axis, deeper and more comprehensive studies will be needed to confirm these associations and to characterize the underlying molecular mechanisms.

Keywords

• enfermedades del sistema nervioso, hormona folículo estimulante, hormona luteinizante, sistema hipotálamo-hipofisário, testosterona