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The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.
Bertoldo, E, Adami, G, Rossini, M, Giollo, A, Orsolini, G, Viapiana, O, Gatti, D, Fassio, A
Frontiers in endocrinology. 2021;:620920
Abstract
The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.
2.
Effect of estrogen-active compounds on the expression of RACK1 and immunological implications.
Buoso, E, Masi, M, Galbiati, V, Maddalon, A, Iulini, M, Kenda, M, Sollner Dolenc, M, Marinovich, M, Racchi, M, Corsini, E
Archives of toxicology. 2020;(6):2081-2095
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Abstract
We previously demonstrated the existence of a balance among steroid hormones, i.e. glucocorticoids and androgens, in RACK1 (receptor for activated C kinase 1) expression and innate immunity activation, which may offer the opportunity to use RACK1 expression as marker to evaluate immunotoxicity of hormone-active substances. Because of the existence of close interconnections between the different steroid hormone receptors with overlapping ligand specificities and signaling pathways, in this study, we wanted to investigate a possible effect of estrogenic active compounds, namely 17β-estradiol, diethylstilbestrol, and zearalenone, on RACK-1 expression and innate immune responses using THP-1 cells as experimental model. All compounds increased RACK1 transcriptional activity as evaluated by reporter luciferase activity, mRNA expression as assessed by real time-PCR and protein expression by western blot analysis, which paralleled an increase in LPS-induced IL-8, TNF-α production, and CD86 expression, which we previously demonstrated to be dependent on RACK1/PKCβ activation. As the induction of RACK1 expression can be blocked by the antagonist G15, induced by the agonist G1 and by the non-cell permeable 17β-estradiol conjugated with BSA, a role of GPER (previously named GPR30) activation in estrogen-induced RACK1 expression could be demonstrated. In addition, a role of androgen receptor (AR) in RACK1 transcription was also demonstrated by the ability of flutamide, a nonsteroidal antiandrogen, to completely prevent diethylstilbestrol-induced RACK1 transcriptional activity and protein expression. Altogether, our data suggest that RACK1 may represent an interesting target of steroid-active compounds, and its evaluation may offer the opportunity to screen the immunotoxic potential of hormone-active substances.
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The Microbiome-Estrogen Connection and Breast Cancer Risk.
Parida, S, Sharma, D
Cells. 2019;(12)
Abstract
The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.
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Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues.
Morani, A, Warner, M, Gustafsson, JA
Journal of internal medicine. 2008;(2):128-42
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Abstract
For the past 10 years it is known that oestrogen functions through the activation of two oestrogen receptors (ERalpha and ERbeta). To the great surprise of endocrinologists, ERbeta was found to be widely distributed in tissues throughout the body including tissues previously considered as 'oestrogen insensitive'. The epithelium of the ventral prostate and lung as well as ovarian granulosa cells are ERalpha-negative but ERbeta-positive and in these tissues ERbeta seems to be involved in important physiological processes, like differentiation, extracellular matrix organization and stromal-epithelial communication. In tissues where both ERs are expressed, the two receptors seem to counteract each other. In the uterus, mammary gland and immune system, ERalpha promotes proliferation whereas ERbeta has pro-apoptotic and pro-differentiating functions. The challenge of the future will be to develop specific agonists, which can selectively activate/inactivate either ERalpha or ERbeta. These pharmaceuticals are likely to be of clinical importance in the prevention or treatment of various diseases.