Gaberšček Simona, Zaletel Katja, Schwetz Verena, Pieber Thomas, Obermayer-Pietsch Barbara, Lerchbaum Elisabeth
Department of Nuclear MedicineUniversity Medical Centre Ljubljana, Zaloška 7, 1525 Ljubljana, SloveniaFaculty of MedicineUniversity of Ljubljana, Vrazov trg 2, 1104 Ljubljana, SloveniaDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria Department of Nuclear MedicineUniversity Medical Centre Ljubljana, Zaloška 7, 1525 Ljubljana, SloveniaFaculty of MedicineUniversity of Ljubljana, Vrazov trg 2, 1104 Ljubljana, SloveniaDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Department of Nuclear MedicineUniversity Medical Centre Ljubljana, Zaloška 7, 1525 Ljubljana, SloveniaFaculty of MedicineUniversity of Ljubljana, Vrazov trg 2, 1104 Ljubljana, SloveniaDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Eur J Endocrinol. 2015 Jan;172(1):R9-21. doi: 10.1530/EJE-14-0295.
Thyroid disorders, especially Hashimoto's thyroiditis (HT), and polycystic ovary syndrome (PCOS) are closely associated, based on a number of studies showing a significantly higher prevalence of HT in women with PCOS than in controls. However, the mechanisms of this association are not as clear. Certainly, genetic susceptibility contributes an important part to the development of HT and PCOS. However, a common genetic background has not yet been established. Polymorphisms of the PCOS-related gene for fibrillin 3 (FBN3) could be involved in the pathogenesis of HT and PCOS. Fibrillins influence the activity of transforming growth factor beta (TGFβ). Multifunctional TGFβ is also a key regulator of immune tolerance by stimulating regulatory T cells (Tregs), which are known to inhibit excessive immune response. With lower TGFβ and Treg levels, the autoimmune processes, well known in HT and assumed in PCOS, might develop. In fact, lower levels of TGFβ1 were found in HT as well as in PCOS women carrying allele 8 of D19S884 in the FBN3 gene. Additionally, vitamin D deficiency was shown to decrease Tregs. Finally, high estrogen-to-progesterone ratio owing to anovulatory cycles in PCOS women could enhance the immune response. Harmful metabolic and reproductive effects were shown to be more pronounced in women with HT and PCOS when compared with women with HT alone or with controls. In conclusion, HT and PCOS are associated not only with respect to their prevalence, but also with regard to etiology and clinical consequences. However, a possible crosstalk of this association is yet to be elucidated.
基于多项研究表明，多囊卵巢综合征（PCOS）女性中桥本甲状腺炎（HT）的患病率显著高于对照组，甲状腺疾病，尤其是HT，与PCOS密切相关。然而，这种关联的机制尚不清楚。当然，遗传易感性在HT和PCOS的发生发展中起重要作用。然而，尚未确定共同的遗传背景。与PCOS相关的原纤蛋白3（FBN3）基因多态性可能参与了HT和PCOS的发病机制。原纤蛋白影响转化生长因子β（TGFβ）的活性。多功能TGFβ也是免疫耐受的关键调节因子，它通过刺激调节性T细胞（Tregs）发挥作用，已知Tregs可抑制过度的免疫反应。随着TGFβ和Tregs水平降低，HT中众所周知的自身免疫过程以及PCOS中推测的自身免疫过程可能会发展。事实上，在携带FBN3基因D19S884等位基因8的HT患者以及PCOS女性中均发现TGFβ1水平较低。此外，维生素D缺乏被证明会减少Tregs。最后，PCOS女性无排卵周期导致的高雌激素与孕酮比值可能会增强免疫反应。与单纯患有HT的女性或对照组相比，HT和PCOS女性的有害代谢和生殖影响更为明显。总之，HT和PCOS不仅在患病率方面相关，在病因和临床后果方面也相关。然而，这种关联可能存在的相互作用尚待阐明。
