Rheumatic diseases and Klinefelter's syndrome

Rovenský, Jozef; Imrich, Richard; Lazúrová, Ivica; Payer, Juraj

doi:10.1111/j.1749-6632.2009.05292.x

Cited by 38 publications

(4 citation statements)

References 41 publications

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“…As far as the male population is concerned, the literature is almost non-existent. An increased incidence of autoimmune diseases is reported in subjects affected by KS [ 87 , 88 , 89 ]. However, whether the autoimmune activation is secondary to the decreased testosterone levels per se, or the increased gonadotropin levels is not yet fully understood.…”

Section: Extra-gonadal Effects Of Fshmentioning

confidence: 99%

Extra-Gonadal and Non-Canonical Effects of FSH in Males

et al. 2023

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Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a β subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.

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Section: Extra-gonadal Effects Of Fshmentioning

confidence: 99%

Extra-Gonadal and Non-Canonical Effects of FSH in Males

et al. 2023

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“…By perturbing the expression of Xist in a mouse model, a recent study proposed a direct link between dysregulated XCI and the development of autoimmunity (Huret et al, 2023). Furthermore, males with Klinefelter syndrome, who have one or more additional X chromosomes, have an increased risk of developing humoral autoimmune disorders such as SLE (Scofield et al, 2008;Dillon et al, 2011), systemic sclerosis (Rovenský et al, 2014) and Sjögren's Disease (V. M. Harris et al, 2016), despite the presence of male sex hormones.…”

Section: Introductionmentioning

confidence: 99%

Oestrogen influences B cell class-switching in individuals with an XX sex chromosome complement

Peckham,

Radziszewska,

de Gruijter

et al. 2024

Preprint

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Sex differences in humoral immunity are well-documented, though the mechanisms underpinning these differences remain ill-defined. Here, we demonstrate that post-pubertal cisgender females have higher levels of class-switched B cells compared to age-matched cisgender males. However, whilst sex chromosome-encoded genes characterise most of the differences in total B cell transcriptomes between cisgender-females and -males, sex differences in class-switched B cells are only observed post-pubertally. Accordingly, B cells express high levels of oestrogen receptor 2 (ESR2) and genes known to regulate B cell class-switching are enriched for ESR2-binding sites. Using a gender-diverse cohort of young people, we show that in transgender males (XX chromosomal background), blockade of natal oestrogen reduced the frequency of class-switched B cells, whilst gender-affirming oestradiol treatment in transgender females (XY chromosomal background), did not increase the frequency of class-switched B cells. These data demonstrate that sex hormones and chromosomes work in tandem to impact immune responses, with oestrogen only supporting B cell class-switching on an XX chromosomal background.

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“…Firstly, KS men tend to have a body fat distribution more akin to women and many experience gynecomastia (Smyth & Bremner, 1998). Secondly, numerous lines of evidence indicate that being XXY may be a risk factor for other autoimmune diseases, which are typically strongly female-biased (Oktenli et al, 2002; Rovensky, Imrich, Lazurova, & Payer, 2010). For instance, the risk of systemic lupus erythematosus (SLE) in KS men is ∼14-fold higher than in 46, XY men—a relative risk similar to that of 46, XX women (Scofield et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Feminized Behavior and Brain Gene Expression in a Novel Mouse Model of Klinefelter Syndrome

et al. 2014

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Klinefelter Syndrome is the most common sex chromosome aneuploidy in men and is characterized by the presence of an additional X chromosome (XXY). In some Klinefelter males, certain traits may be feminized or shifted from the male-typical pattern towards a more female-typical one. Among them might be partner choice, one of the most sexually dimorphic traits in the animal kingdom. We investigated the extent of feminization in XXY male mice (XXYM) in partner preference and gene expression in the bed nucleus of the stria terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy model. We tested for partner preference using a three-chambered apparatus in which the test mouse was free to choose between stimulus animals of either sex. We found that partner preference in XXYM was feminized. These differences were likely due to interactions of the additional X chromosome with the Y. We also discovered genes that differed in expression in XXYM vs. XYM. Some of these genes are feminized in their expression pattern. Lastly, we also identified genes that differed only between XXYM vs. XYM and not XXM vs. XYM. Genes that are both feminized and unique to XXYM vs. XYM represent strong candidates for dissecting the molecular pathways responsible for phenotypes present in KS/XXYM but not XXM. In sum, our results demonstrated that investigating behavioral and molecular feminization in XXY males can provide crucial information about the pathophysiology of Klinefelter Syndrome and may aid our understanding of sex differences in brain and behavior.

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Rheumatic diseases and Klinefelter's syndrome

Cited by 38 publications

References 41 publications

Extra-Gonadal and Non-Canonical Effects of FSH in Males

Extra-Gonadal and Non-Canonical Effects of FSH in Males

Oestrogen influences B cell class-switching in individuals with an XX sex chromosome complement

Feminized Behavior and Brain Gene Expression in a Novel Mouse Model of Klinefelter Syndrome

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