Sex steroids in Sjögren’s syndrome

Konttinen, Yrjö T.; Fuellen, Georg; Yan, Bing; Porola, Pauliina; Stegaev, Vasily; Trokovic, Nina; Falk, Steffi; Liu, Yi; Szodoray, Péter; Takakubo, Yuya

doi:10.1016/j.jaut.2012.01.004

Cited by 59 publications

(33 citation statements)

References 27 publications

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“…The role of sex steroids in SS onset and maintenance has been ascertained, [93][94][95][96] although impairment of other endocrine circuits (including the hypothalamic-pituitary-adrenal/gonadal/thyroid axis and the growth hormone/insulin growth factor-1 axis) plays an important role, 97 and other elements, such as a genetic predisposition, may also be necessary as not all post-menopausal women develop the disease. 98 Lower levels of the sex-steroid precursors DHEA and DHEA-S were shown in blood and saliva of SS patients 99-101 compared with healthy controls and as a consequence of aging.…”

Section: Gender Sex Steroids and Aqueous-deficient De -Sjogren's Synmentioning

confidence: 99%

Sex-Steroid Imbalance in Females and Dry Eye

Versura

Giannaccare

Campos

2014

Current Eye Research

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Dry eye (DE) is a multifactorial disorder of the ocular surface unit that results in eye discomfort, visual disturbance and ocular surface damage. It is one of the most common complaints in daily ophthalmic practice. The risk of DE increases with age in both sexes, while its incidence is higher among females. In addition, the condition of menopause in aging women may also contribute to DE onset or worsening as a consequence of an overall hormonal imbalance. Sex hormones play a key role in ocular surface physiology and they impact differently on ocular surface tissues. Reduced estrogen levels were historically thought to be responsible in age-related DE onset but more recent investigations have reconsidered the role of androgens that are present and exert a protective function on the ocular surface. Hormone levels themselves, withdrawal changes in hormone levels, and the changes in hormone-receptor responsiveness are all important factors but it remains to be fully elucidated how estrogen or androgen insufficiency act alone or together in a combined imbalance or interplay to raise the risk of disease. The purpose of this review is to briefly outline current scientific evidence on the influence of androgens and estrogens, on the Lachrymal and Meibomian glands and on ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. The role of sex steroids is also discussed in relation to the pathogenesis of different forms of DE and Sjogren's syndrome (SS). The impact of systemic hormone therapy (HT) in DE post-menopausal women still appears as a controversial issue, despite the many clinical studies. Finally, the outcomes of topical applications of steroid-based products are summarized, underlying the need for potential (tear) biomarker(s) in the rationale of DE-targeted therapy.

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Section: Gender Sex Steroids and Aqueous-deficient De -Sjogren's Synmentioning

confidence: 99%

Sex-Steroid Imbalance in Females and Dry Eye

Versura

Giannaccare

Campos

2014

Current Eye Research

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“…This prevalence has been linked to estrogen status. Investigators have proposed that estrogens positively modulate the structure, function and secretion of the lacrimal gland and that estrogen deficiency leads to numerous lacrimal gland sequelae, including acinar cell disruption, apoptosis and necrosis, cellular vacuolization, DNA degradation, inflammation, glandular regression and aqueous-deficient dry eye (Azzarolo et al, 2003; Konttinen et al, 2012; Mostafa et al, 2012; Song et al, 2012; Sullivan, 2004 1 ). Researchers have also posited that estrogen insufficiency promotes a SjS-like autoimmune exocrinopathy (Arakaki et al, 2010; Hayashi et al, 2004; Ishimaru et al, 2003; Ishimaru et al, 1999; Shim et al, 2004; Sullivan, 2004; Takahashi et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Darabad¹,

Suzuki²,

Richards³

et al. 2014

Experimental Eye Research

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Researchers have proposed that estrogen deficiency will lead to a Sjögren's syndrome (SjS)-like lacrimal gland inflammation, aqueous tear deficiency and dry eye. The purpose of this study was to determine whether this proposal is correct. Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice, in which estrogen synthesis is completely eliminated. Tissues were also obtained from autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice as inflammation controls. Tear volumes in WT and ArKO mice were measured and glands were processed for molecular biological and histological evaluation. Our results demonstrate that estrogen absence does not lead to a SjS-like inflammation in lacrimal tissue or to an aqueous-deficient dry eye. There was no upregulation of genes associated with inflammatory pathways in lacrimal glands of male or female ArKO mice. Such inflammatory activity was prominent in autoimmune MRL/lpr tissues. We also found no evidence of inflammation in lacrimal gland tissue sections of estrogen-deficient mice, and tear volumes of ArKO males were actually increased as compared to those WT controls. Interestingly, our study did show that estrogen absence influences the expression of thousands of lacrimal gland genes, and that this impact is sex- and genotype-specific. Our findings demonstrate that estrogen absence is not a risk factor for the development of SjS-like lacrimal gland inflammation or for aqueous-deficient dry eye in mice.

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“…The role of androgen on the immune response is still controversial but generally it is thought to exert suppressive potential2627. Studies have indicated that, like estrogen, androgen has an important role in preventing apoptosis of gland epithelium and in SjS glands2829. When androgen regulation is defective, acinar atrophy and ductal cell hyperplasia can occur30.…”

mentioning

confidence: 99%

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

Voigt

Esfandiary

Wanchoo

et al. 2016

Sci Rep

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Interleukin (IL)-17 is one of the critical inflammatory cytokines that plays a direct role in development of Sjögren’s syndrome (SjS), a systemic autoimmune disease characterized by a progressive chronic attack against the exocrine glands. The expression levels of IL-17 are correlated with a number of essential clinical parameters such as focus score and disease duration in human patients. Significantly immunological differences of Th17 cells were detected at the onset of clinical disease in female SjS mice compared to males. To further define the role of IL-17 in SjS and elucidate its involvement in the sexual dimorphism, we examined the systemic effect of IL-17 by genetically ablating Il-17 in the C57BL/6.NOD-Aec1Aec2, spontaneous SjS murine model. The results indicate that IL-17 is a potent inflammatory molecule in the induction of chemoattractants, cytokines, and glandular apoptosis in males and females. Elimination of IL-17 reduced sialadenitis more drastically in females than males. IL-17 is highly involved in modulating Th2 cytokines and altering autoantibody profiles which has a greater impact on changing plasma cells and germinal center B cell populations in females than males. The result supports a much more important role for IL-17 and demonstrates the sexual dimorphic function of IL-17 in SjS.

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Sex steroids in Sjögren’s syndrome

Cited by 59 publications

References 27 publications

Sex-Steroid Imbalance in Females and Dry Eye

Sex-Steroid Imbalance in Females and Dry Eye

Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome

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