1,356,359 research outputs found
Modena MG, Sismondi P, Mueck AO, Kuttenn F, Lignières B, Verhaeghe J, Foidart JM, Caufriez A, Genazzani AR; TREAT.
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Non-genomic actions of sex steroid hormones
No full textSteroid hormone receptors have been traditionally considered to act via the regulation of transcriptional processes, involving nuclear translocation and binding to specific response elements, and ultimately leading to regulation of gene expression. However, novel non-transcriptional mechanisms of signal transduction through steroid hormone receptors have been identified. These so-called 'non-genomic' effects do not depend on gene transcription or protein synthesis and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Several relevant biological actions of steroids have been associated with this kind of signaling. Ubiquitous regulatory cascades such as mitogen-activated protein kinases, the phosphatidylinositol 3-OH kinase and tyrosine kinases are modulated through non-transcriptional mechanisms by steroid hormones. Furthermore, steroid hormone receptor modulation of cell membrane-associated molecules such as ion channels and G-protein-coupled receptors has been shown. TIssues traditionally considered as 'non-targets' for classical steroid actions are instead found to be vividly regulated by non-genomic mechanisms. To this aim, the cardiovascular and the central nervous system provide excellent examples, where steroid hormones induce rapid vasodilatation and neuronal survival via non-genomic mechanisms, leading to relevant pathophysiological consequences. The evidence collected in the past Years indicates that target cells and organs are regulated by a complex interplay of genomic and non-genomic signaling mechanisms of steroid hormones, and the integrated action of these machineries has important functional roles in a variety of pathophysiological processes. The understanding of the molecular basis of the rapid effects of steroids is therefore important, and may in the future turn out to be of relevance for clinical purposes
Might DHEA be Considered a Beneficial Replacement Therapy in the Elderly ?
No full textDehydroepiandrosterone (DHEA) [prasterone] is typically secreted by the adrenal glands and its secretory rate changes throughout the human lifespan.When human development is completed and adulthood is reached, DHEA and DHEA sulphate (DHEAS) [PB-008] levels start to decline so that at 70–80 years of age, peak DHEAS concentrations are only 10–20% of those in young adults.This age-associated decrease has been termed ‘adrenopause’, and since many agerelated disturbances have been reported to begin with the decline of DHEA/DHEAS levels, this provides a potential opportunity for use of DHEA as replacementtherapy.For these reasons, use of DHEA as a replacement therapy in aging men and women has been proposed and this paper outlines the reported beneficial effects ofsuch treatment in humans. Many interesting results have been obtained in experimental animals suggesting that DHEA positively modulates most age-related disturbances. However, renewed interest in DHEA has arisen as a result of recentstudies suggesting that DHEA appears to be beneficial in hypoandrogenic men as well as in postmenopausal and aging women. Menopause is the event in awoman’s life that induces a dramatic change in the steroid milieu, and use of DHEA as ‘replacement treatment’ has been reported to restore both the androgenic and estrogenic environment and reduce most of the symptoms of this change.As menopause is the beginning of the biological transition of women towards senescence, it is of great interest to better understand how DHEA might help to solve and/or overcome the problems of this complex stage of life. In men withadrenal insufficiency and hypogonadism without androgen replacement, DHEA administration results in a significant increase in circulating androgens.Though most data are suggestive for use of DHEA as hormonal replacement treatment, more defined and specific clinical trials are needed to uncover all of the ‘secrets’ and features of this steroid before it can be used as a standard treatment.Furthermore, DHEA is perceived differently around the world, being considered only a ‘dietary supplement’ in the US, while in many European countries it isconsidered a ‘true hormone’ that has not been approved for use as a hormonal treatment by the European health authorities. This overview offers some points of view on use of DHEA as an experimental hormonal replacement therapy
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