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  • 1
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 97, No. 4 ( 2012-04), p. 1311-1319
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2012
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  • 2
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 3, No. Supplement_1 ( 2019-04-15)
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
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  • 3
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Recent studies showed that various factors, including age, gender, race, iodine intake, obesity, the thyroid peroxidase antibody (TPO-Ab), and/or smoking, influence the thyroid status. In the present study, we analyzed and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab) in Japanese euthyroxinemia individuals with serum free T4 level within normal range. A total of 12,289 subjects who underwent health check-ups were analyzed in a cross-sectional and longitudinal study. The mean age of subjects was 50 ± 10 years (age range: 21–88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese euthyroxinemia subjects. Mean and median serum TSH levels increased with age in smokers and non-smokers, but were significantly lower in smokers than in non-smokers among men and women in most age groups; the median 97.5th percentiles of TSH levels were 1.2 mU/liter and 2.9 mU/liter in smokers, and 1.4 mU/liter and 3.9 mU/liter in non-smokers in 31- to 40-year-old men, p & lt;0.01, and 1.4mU/liter and 4.3 mU/liter, and 1.8mU/liter and 6.2 mU/liter in 61- to 70-year-old men, p & lt;0.01. However, smoking had a negligible effect on serum TSH levels in women older than 50 years; 1.3 mU/liter in smokers and 1.6 mU/liter in non-smokers in 31- to 40-year-old women, p & lt;0.01, and 1.5 mU/liter and 1.8 mU/liter in 51- to 60-year-old women, p=0.3. Furthermore, the present study confirmed that serum free T4 levels in men progressively decreased with age, whereas no significant change was observed in women. Smoking did not affect the relationship between age and serum free T4 levels in men or women, except for men in their 20s. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both genders; however, smoking did not affect free T4 levels or the positivity for TPO-Ab. The rate of smokers in men was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%, p & lt;0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels one year after the start of smoking in men (p & lt;0.05). Since smoking appears to lower serum TSH levels in Japanese euthyroxinemia subjects careful consideration of the smoking status is needed when evaluating subclinical thyroid function.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
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  • 4
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    The Endocrine Society ; 2020
    In:  Journal of the Endocrine Society Vol. 4, No. 7 ( 2020-07-01)
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. 7 ( 2020-07-01)
    Abstract: Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes and recycle their metabolites. We have recently demonstrated the crucial role for the basal level of autophagic activity in thyrocyte survival and homeostasis using the thyroid-specific autophagy knockout mice. Here, we first studied hormonal regulation of autophagy in thyrocytes in vitro using a rat thyroid cell line PCCl3 and in vivo with mice. In cultured PCCl3 cells, thyroxine decreased microtubule-associated protein 1 light chain 3 (LC3) puncta (a component of autophagosome) and increased p62 (an autophagy substrate) levels, showing thyroxine-suppression of autophagy. In contrast, TSH increased both LC3 puncta and p62 levels, but at the same time stabilized p62 protein by inhibiting p62 degradation, indicating TSH induction of autophagy. Our experiments with various inhibitors identified that both the cAMP-protein kinase (PK) A-cAMP response element binding protein/ERK and PKC signaling pathways regulates positively autophagic activity. The in vivo results obtained with wild-type mice treated with methimazole and perchlorate or thyroxine were consistent with in vitro results. Next, in thyroid-specific autophagy knockout mice treated with methimazole and perchlorate (that is, mice were placed under a stressed condition where enhanced autophagy was required) for 2 months, lower follicle sizes and lower thyroglobulin contents in thyrocytes were observed, suggesting impaired thyroglobulin production presumably from insufficient nutrient supply. We therefore conclude that TSH positively regulates autophagic activity through the cAMP-PKA-cAMP response element binding protein/ERK and PKC signaling pathways, whereas thyroid hormones inhibit its activity in thyrocytes. Metabolites produced by autophagy appear to be necessary for protein synthesis stimulated by TSH.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
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  • 5
    Online Resource
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    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A1021-A1021
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A1021-A1021
    Abstract: Nucleobindin-2 (NUCB2) is a 396-amino acid protein, cleaved into the N-terminal nesfatin-11-82, nesfatin-285-163 and the C-terminal nesfatin-3166-396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+ binding EF-hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin-1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance. There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. NUCB2 was also identified as a potential tumor antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. However, theclinicopathological significance of NUCB2 expression in gastric cancer has still not been elucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathological significance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression-free survival. In summary, NUCB2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 6
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A979-A980
    Abstract: Objective: Thyroid hormones have various effects on cardiac and circulatory systems, leading to arrhythmias and heart failure. In Europe and the United States, it has been reported that elevated thyroid hormones within the normal range have been reported to be associated with a risk of atrial fibrillation, however, there was no report on Japanese cases, a country that differs in iodine intake and ethnicity from the West. Therefore, we evaluated the abnormality of thyroid function in a large number of cases of atrial fibrillation (AF) who received catheter ablation (RFCA) in Japan. Methods: We evaluated 2,937 cases of atrial fibrillation (2,084 males, mean age 64.1±10.7 years and 853 females, 69.0±8.5 years) who underwent RFCA at the Gunma Prefectural Cardiovascular Center between 2012 and 2018. As a control we used a total of 15,660 participants for health check-up (9,176 males, mean age 49.7±9.8 years and 6,484 females, 48.9±10.3 years) from 2006 to 2013, and we evaluated thyroid function after adjusting for gender-specific age. Results: The prevalence of overt hyperthyroidism was significantly higher in the RFCA-treated male group (0.43%) than in the control group (0.07%), even after adjusting for age (p & lt;0.01). Similarly, the prevalence of subclinical hyperthyroidism was also significantly higher in the RFCA-treated male group (3.12%) than in the control group (0.94%) after adjusting for age (p & lt;0.01). On the other hand, subclinical hypothyroidism was significantly lower in the RFCA-treated group after adjusting for age (2.97% in the RFCA-treated group and 3.93% in the control group, p & lt;0.01). Females showed the same results as males. Conclusions: In an iodine rich country Japan, not only overt hyperthyroidism but also subclinical hyperthyroidism is an obvious risk factor for severe atrial fibrillation in Japan. Intriguingly, subclinical hypothyroidism might contribute to the prevention of atrial fibrillation, suggesting that slightly higher serum TSH levels might be better for elderlies.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 7
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A851-A851
    Abstract: Objectives: The hypothalamic-pituitary-thyroid (HPT) axis plays a significant role in the regulation of energy expenditure. Previous reports demonstrated that thyroid hormones are critically involved in metabolic process, and hypothyroidism was induced by fasting. The mechanism by which TRH neurons sense alterations in peripheral energy stores is supposed to be regulated by leptin, an adipose tissue-derived hormone. Leptin was initially considered as a hormone to prevent obesity, it was later showed that the major role of leptin is to signal the switch from the fed to the starved state at the hypothalamic level. Recently, we generated TRH-deficient mice (TRH-/-). The mice exhibit tertiary/central hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. In this study, we used TRH-/- to investigate the physiological role of TRH in fasting energy expenditure, including the mechanism regulated by leptin. Methods: Twelve-week-old male F2 hybrid ICR mice were used in this study. (1) Wild-type mice (WT) and TRH-/- were fasted up to 50 hrs. Blood samples were collected from tail veins at various points. Anterior pituitary samples were obtained from euthanized mice before and after 16 hrs fasting. (2) Serum free T4 (FT4) and TSH levels assessed. (3) The expression level of TSHβ mRNA in anterior pituitary were detected using qPCR assays. (4) We repeated these experiments using mice with leptin administration; leptin (0.5μg/g•BW) was administrated every 6 hours starting at after 2 hours fasting. Results: In WT, the level of FT4 was decreased chronologically during fasting to approximately 50% at 50 hrs after fasting. Serum TSH decreased to 70% and the expression level of TSHβ mRNA in anterior pituitary also decreased to 30% compared to before fasting. Administration of leptin recovered the level of FT4 to basal level. However, the level of serum TSH and TSHβ mRNA in pituitary were not recovered to basal levels. By contrast, in TRH-/-, the level of FT4 were also decreased after fasting indicating that the decrease of FT4 by fasting was independent of TRH. However, the level of FT4 was not recovered by leptin suggesting that the recovery of FT4 by leptin was TRH dependent. Serum TSH level decreased to 75% after fasting, and no recovery to basal level with leptin administration was observed in TRH-/- same as WT. In TRH-/-, the pituitary TSHβ mRNA expression level was about 50% of WT before fasting. It did not correlate with the serum TSH level. In addition, no increase in TSHβ mRNA expression level by leptin administration was observed in TRH-/-. These findings suggested that the TSHβ mRNA expression level in the pituitary is completely TRH-dependent in TRH-/-. Conclusion: Fasting-induced hypothyroxinemia was independent of TRH. Leptin regulates H-P-T axis via TRH during fasting-induced energy expenditure. Leptin may modulate the biological activity of TSHβ.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 8
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 96, No. 8 ( 2011-08), p. 2512-2518
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2011
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  • 9
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 98, No. 8 ( 2013-08-01), p. 3280-3287
    Abstract: Subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) increase with age; however, their relationship remains unclear. Objective: Our objective was to investigate the relationship between SCH and indices of metabolic syndrome and follow up subjects for 1 year. Design: Cross-sectional and longitudinal follow-up studies of cases were collected from Takasaki Hidaka Hospital between 2003 and 2007. Participants: Overall, 11 498 participants of health checkups were analyzed. The mean age was 48 ± 9 years. Main Outcome Measures: The relationship between SCH and indices of MetS were examined. Results: Serum free T4 levels were lower in women than men in most of the age groups, and the prevalence of SCH, 6.3% in women vs 3.4% in men, increased with age, reaching 14.6% in 70-year-old women. Multivariate logistic-regression analyses revealed that waist circumference and the serum triglyceride and low-density lipoprotein-cholesterol levels were significantly higher in subjects with SCH than without among women. Reflecting these findings, the adjusted odds ratio of MetS in patients with SCH was higher than in the euthyroid subjects in women with an odds ratio of 2.7 (95% confidence interval 1.1–5.6; P = .017) but not in men. Furthermore, progression from euthyroid into SCH resulted in a significant increase in the serum triglyceride levels but not low-density lipoprotein-cholesterol in women. Conclusion: Japanese women exhibited a high prevalence of SCH associated with low free T4 levels. There was a strong association between SCH and several indices of metabolic syndrome in women. SCH may affect serum triglyceride levels and be a risk factor for metabolic syndrome.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2013
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  • 10
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 10 ( 2019-10-01), p. 4879-4888
    Abstract: The most frequent cause of central hypothyroidism (CeH) is pituitary adenomas, but the mechanisms remain unclear. Objective We investigated serum thyroid levels and GH/IGF-1 in central hypothyroidism in untreated patients with pituitary nonfunctioning and GH-secreting adenomas. Design This was a retrospective cross-sectional study of cases collected from Gunma University and Toranomon Hospitals between 2007 and 2016. Patients One-hundred thirty-nine cases of nonfunctioning pituitary adenoma (NFPA) and 150 cases of GH-secreting pituitary adenoma (GHPA) were analyzed. Main Outcome Measures The correlations between thyroid levels, several clinicopathological parameters, and GH/IGF-1 were examined. Results Twenty-four percent of NFPA patients had CeH. The severity did not correlate with tumor size, age, or sex, and all cases had normal TSH levels. In contrast, only 8.7% of GHPA patients had CeH; approximately half had normal TSH levels and approximately half had low TSH levels. Serum TSH levels in GHPA patients were significantly lower and free T4 (FT4) and free T3 levels were higher than those in patients with NFPA. Furthermore, approximately one-fourth of GHPA patients had normal FT4 and low TSH levels. In addition, serum FT4 levels and serum TSH levels were positively and negatively correlated, respectively, with serum IGF-1 levels. Furthermore, IGF-1 levels in patients with GHPA decreased with age. Conclusions (i) NFPA patients with CeH had TSH levels within a normal range. (ii) GHPA patients had a low incidence of CeH, which may be a result of stimulated thyroid function by GH/IGF-1. (iii) We found an age-dependent decrease in serum IGF-1 levels in patients with GHPA.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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