The role of the thyroid in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS

Functional imaging of interleukin 1 beta expression in inflammatory process using bioluminescence imaging in transgenic mice

<p>Abstract</p> <p>Background</p> <p>Interleukin 1 beta (IL-1β) plays an important role in a number of chronic and acute inflammatory diseases. To understand the role of IL-1β in disease processes and develop an <it>in vivo </it>screening system for anti-inflammatory drugs, a transgenic mouse line was generated which incorporated the transgene firefly luciferase gene driven by a 4.5-kb fragment of the human IL-1β gene promoter. Luciferase gene expression was monitored in live mice under anesthesia using bioluminescence imaging in a number of inflammatory disease models.</p> <p>Results</p> <p>In a LPS-induced sepsis model, dramatic increase in luciferase activity was observed in the mice. This transgene induction was time dependent and correlated with an increase of endogenous IL-1β mRNA and pro-IL-1β protein levels in the mice. In a zymosan-induced arthritis model and an oxazolone-induced skin hypersensitivity reaction model, luciferase expression was locally induced in the zymosan injected knee joint and in the ear with oxazolone application, respectively. Dexamethasone suppressed the expression of luciferase gene both in the acute sepsis model and in the acute arthritis model.</p> <p>Conclusion</p> <p>Our data suggest that the transgenic mice model could be used to study transcriptional regulation of the IL-1β gene expression in the inflammatory process and evaluation the effect of anti-inflammatory drug <it>in vivo</it>.</p

Overexpression of Parkin Ameliorates Dopaminergic Neurodegeneration Induced by 1- Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mice

<div><p>Mutations in the <em>parkin</em> gene are currently thought to be the most common cause of recessive familial Parkinsonism. Parkin functions as an E3 ligase to regulate protein turnover, and its function in mitochondrial quality control has been reported recently. Overexpression of parkin has been found to prevent neuronal degeneration under various conditions both in vivo and in vitro. Here, we generated a transgenic mouse model in which expression of wild type parkin was driven by neuron-specific enolase (NSE) promoter. We reported that both young and old parkin transgenic mice exhibited less reduction of striatal TH protein and number of TH positive neurons in the substantia nigra induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP), compared to wild type littermates. MPTP-induced mitochondrial impairment in the substantia nigra was improved in young parkin transgenic mice. Decreased striatal α-synuclein was demonstrated in old parkin transgenic mice. These results provide reliable evidence from the transgenic mouse model for parkin that overexpression of parkin may attenuate dopaminergic neurodegeneration induced by MPTP through protection of mitochondria and reduction of α-synuclein in the nigrostriatal pathway.</p> </div

Levels of α-synuclein protein expression in the striatum of wild type and parkin transgenic mice.

<p>Western blot showing α-synuclein protein in the striatum of young (A) and old (C) mice after saline or MPTP treatment. (B, D) Quantification of relative α-synuclein protein expression. Data presented are the means±SE. # p<0.05, significant differences between wild type and transgenic mice; n = 4−6 per group.</p

Transcriptional expression of bcl-2, bax, PINK1 and DJ-1 in the substantia nigra.

<p>Samples were from young and old mice treated with MPTP or saline. mRNA expression levels of bcl-2 (A), bax (B), PINK1 (C), DJ-1 (D) were determined by real-time PCR and normalized to GAPDH. Values are means±SE. *p <0.05, significant differences between saline and MPTP-treated mice; #p<0.05, significant differences between wild type and transgenic mice; n = 4−7 per group.</p

No changes of Hsp70 protein expression in the striatum of wild type and parkin transgenic mice.

<p>Western blot showing Hsp70 protein in the striatum of young (A) and old (C) mice after saline or MPTP treatment. Quantification of relative Hsp70 protein expression shown in B, D. Data presented are the means±SE. n = 4−6 per group.</p

Less morphological damage of mitochondria in the SNpc neurons of parkin transgenic mice induced by MPTP.

<p>Electron microscopy showing the morphology of mitochondria in the SNpc from young mice at 3 days after MPTP (A, B) or saline treatment (C, D). (A, C) wild type mice; (B, D) parkin transgenic mice. Arrows represent abnormal mitochondria with numerous vacuoles and fragmented cristae; Triangles represent normal mitochondria. (E) Quantitative analyses of the percentage of damaged mitochondria in the SNpc neurons. Scale bar, 1 μm; Data presented are the means±SE. *p <0.05, significant differences between saline and MPTP-treated mice; n = 3 per group.</p

MPTP elicited less dopaminergic toxicity in parkin transgenic mice.

<p>Samples were collected at 1 day or 3 days from the striatum (A, B) and the substantia nigra (C, D) after saline or MPTP treatment. Western blot showing striatal TH protein expression in young (A-a) and old (B-a) mice. Quantification of relative TH protein expression was showed in the right panel. Immunohistochemical staining of the striatum showing TH positive nerve fibers of young (A-b) and old (B-b) mice. Scale bar, 0.2 mm. Relative optical density of the staining was showed in the right panel. Immunohistochemical staining showing TH positive cells in the substantia nigra of young (C) and old (D) mice. The sections were from wild type (a, b, c) or parkin transgenic (d, e, f) mice; (a, d) saline; (b, e) 1 day after MPTP treatment; (c, f) 3 days after MPTP treatment. Images to the right are higher magnification of the SN sections. Statistical data of the number of TH positive neurons (left panel) and nissl positive neurons (right panel) were showed in the bottom. Scale bar, 20 µm. Data presented are the means±SE. *p <0.05 and * *p <0.01, significant differences between saline and MPTP-treated mice; #p<0.05 and # #p<0.01, significant differences between wild type and transgenic mice; n = 3−6.</p