Thyroid Follicular Epithelium Research Articles

Characterization of lesions of nutritional congenital goitre in cattle

There are few studies that classify and characterize the morphometric and immunohistochemical features of goitre in bovine thyroid glands (TGs). We investigated 39 bovine TGs (fetuses [9], stillbirths [18], neonates [12]) born to dams with low T4 hormone levels and no iodine supplementation and 10 (fetuses [3], stillbirths [3], neonates [4]) born to dams with normal T4 levels and supplemented with iodine. Body weight (BW), TG weight (TGW), TGW:BW ratio and histological lesions were determined. The TGs were classified histopathologically as normal gland (G0), mild goitre (G1), moderate goitre (G2) or severe goitre (G3). Various morphological and morphometric parameters were calculated from microscopic images using image analysis software. Immunohistochemistry was performed to detect proliferating cell nuclear antigen (PCNA). There were significant differences in the TGW:BW ratio among groups (P <0.05): 0.3 ± 0.1 in G0, 0.5 ± 0.3 in G1, 0.8 ± 0.3 in G2 and 1.3 ± 0.7 in G3. In G0, large homogeneous follicles with eosinophilic colloid were seen. In the groups with lesions (G1, G2 and G3), heterogeneity in follicle shape and size, height and area of thyroid follicular cells, height of thyroid follicular epithelium and PCNA immunolabelling were directly related to histopathological grade, with significant differences among groups (P <0.001), gradually increasing from G1 to G3 compared with G0. The TGW:BW ratio and histological grade were positively correlated (P = 0.008).

SRPX2 promotes cancer cell proliferation and migration of papillary thyroid cancer

Thyroid cancer is the endocrine tumor with the highest incidence at present. It originates from the thyroid follicular epithelium or follicular paraepithelial cells. There is an increasing incidence of thyroid cancer all over the world. We found that SRPX2 expression level was higher in papillary thyroid tumors than in normal thyroid tissues, and SRPX2 expression was closely related to tumor grade and clinical prognosis. Previous reports showed that SRPX2 could function by activating PI3K/AKT signaling pathway. In addition, in vitro experiments showed that SRPX2 promoted the proliferation and migration of papillary thyroid cancer (PTC). In conclusion, SRPX2 could promote the malignant development of PTC. This may be a potential treatment target for PTC.

Expression of HIF-1α/PKM2 axis correlates to biological and clinical significance in papillary thyroid carcinoma.

hypoxia inducible factor-1α (HIF-1α) and pyruvate kinase M2 (PKM2) are 2 key metabolic regulatory proteins, they could engage in a positive feedback loop and drive cancer growth by enhancing glycolysis. This study aimed to investigate the expression of HIF-1α and PKM2 in papillary thyroid carcinoma (PTC) and its correlation with the patients clinicopathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 60 patients were collected. The expression levels of HIF-1α and PKM2 in PTC tissues were examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between HIF-1α and PKM2 expressions and the clinical pathological features of PTC. The results showed that the positive expressions of HIF-1α, PKM2, and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all significantly higher in PTC than those in normal thyroid follicular epithelium, and a positive correlation was found between HIF-1α and PKM2 in PTC. Further analysis showed that in PTC, the positive expression of HIF-1α and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were significantly associated with bigger tumor size, moreover, the positive expressions of HIF-1α, PKM2 and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all correlated with capsular invasion and lymph node metastasis, while they were all not correlated with gender, sex and multicentricity of tumor. This study identified HIF-1a/PKM2 axis as potential molecular marker for predicting the invasion and progression of papillary thyroid carcinoma.

The effect of acromegaly on thyroid disease.

Long-term stimulation of thyroid follicular epithelium by high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly can lead to thyroid dysfunction, goiter, thyroid nodules, and even thyroid cancer and thyroid-associated ophthalmopathy (TAO). Excessive GH/IGF-1 promotes goiter and thyroid nodule formation, which can be reversed by normalizing the IGF-1 levels with surgery or medical treatment. Whether patients with acromegaly have an increased risk of thyroid cancer remains controversial, and routine thyroid ultrasonography and regular cancer screening are recommended in such cases, especially when the nodules possess malignant propensity. TAO is an autoimmune disease and newer treatments are being discovered against it. Recent studies have reported that the IGF-1 receptor (IGF-1R) plays an important role in the pathogenesis of TAO, and the IGF-1R inhibitor teprotumumab involves significantly improved disease endpoints in patients with active TAO. Thyroid-stimulating hormone (TSH) receptor (TSHR) and IGF-1R co-immunoprecipitate in orbital and thyroid tissues to form a functional complex; thus, combined therapy targeting TSHR and IGF-1R may be more effective than single therapy.

A case report of anaplastic thyroid cancer and papillary thyroid cancer lymph node metastasis: an unusual presentation as an invasive hypopharyngeal mass

Anaplastic thyroid carcinoma is a rare undifferentiated tumour of the thyroid follicular epithelium. It almost always develops from a pre-existing well-differentiated thyroid cancer with a co-existent thyroid malignancy varying from 5 to 17% . The co-existence of papillary thyroid cancer (PTC) with anaplastic thyroid cancer is a rare occurrence in metastases outside the primary thyroid lesion. Traditionally, this has been regarded as an aggressive form of cancer associated with a dismal prognosis. Recently, the focus has shifted to the development of novel therapies based on the availability of comprehensive genomic profiling platforms (CGP) with a rapid turn-around to identify molecular aberrations in tumours which acts as potential therapeutic targets. In the United Kingdom, we report the case of a 60-year-old woman with an unusual presentation of (metastatic) anaplastic thyroid carcinoma and concomitant papillary thyroid cancer metastasis within a contralateral lymph node. This was initially perceived as a left pyriform fossa mass involving and compressing her left hemi-larynx on clinical and radiological examination. Following the identification of BRAF V600E mutation on CGP, she was started on targeted therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib and demonstrated excellent clinical and radiological response following 7 months of treatment. She has subsequently undergone total thyroidectomy alongside with bilateral neck dissection, and is due to start radioactive iodine treatment to reduce the risk of recurrence of disease.

Artificial Intelligence in Toxicological Pathology: Quantitative Evaluation of Compound-Induced Follicular Cell Hypertrophy in Rat Thyroid Gland Using Deep Learning Models.

Digital pathology has recently been more broadly deployed, fueling artificial intelligence (AI) application development and more systematic use of image analysis. Here, two different AI models were developed to evaluate follicular cell hypertrophy in hematoxylin and eosin-stained whole-slide-images of rat thyroid gland, using commercial AI-based-software. In the first, mean cytoplasmic area measuring approach (MCA approach), mean cytoplasmic area was calculated via several sequential deep learning (DL)-based algorithms including segmentation in microanatomical structures (separation of colloid and stroma from thyroid follicular epithelium), nuclear detection, and area measurements. With our additional second, hypertrophy area fraction predicting approach (HAF approach), we present for the first time DL-based direct detection of the histopathological change follicular cell hypertrophy in the thyroid gland with similar results. For multiple studies, increased output parameters (mean cytoplasmic area and hypertrophic area fraction) were shown in groups given different hypertrophy-inducing reference compounds in comparison to control groups. Quantitative results correlated with the gold standard of board-certified veterinary pathologists' diagnoses and gradings as well as thyroid hormone dependent gene expressions. Accuracy and repeatability of diagnoses and grading by pathologists are expected to be improved by additional evaluation of mean cytoplasmic area or direct detection of hypertrophy, combined with standard histopathological observations.

Abstract #1001399: Anaplastic Thyroid Carcinoma as the Etiology of a Rapidly Enlarging Neck Mass

Anaplastic thyroid cancer (ATC) is an undifferentiated tumor of the thyroid follicular epithelium representing approximately 0.5% of clinically recognized thyroid cancers. We present a case of ATC as the cause of a rapidly enlarging neck mass.

Correlation between serum 25-(OH)D3 level and immune imbalance of Th1/Th2 cytokines in patients with Hashimoto's thyroiditis and its effect on autophagy of human Hashimoto thyroid cells.

The study aimed to determine the relationship between serum 25-(OH)D3 and Th1/Th2 cytokine immune imbalance, and the effect of 25-(OH)D3 on the autophagy of human Hashimoto thyroid cells. Western blot analysis was used to detect the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and autophagy-associated protein mammalian target protein of rapamycin (mTOR) in thyroid tissues of 20 Hashimoto's thyroiditis (HT) patients and normal tissues of 20 benign thyroid adenomas. Nthy-ori3-1 cells (normal cells of human thyroid follicular epithelium) were treated with different concentrations of 25-(OH)D3 for 24 h. The expression of LC3, mTOR and caspase-3 protein in the cells was detected by western blot analysis. The apoptosis and proliferation levels were detected by flow cytometry and MTT assay, respectively. The levels of FT3, FT4 and IL-10 in the HT group were lower than those in the healthy control group. The serum levels of 25-(OH)D3, TPOAb and TGAb in the HT group were lower than those in the healthy control group. Serum 25-(OH)D3 level in the HT group was negatively correlated with IL-2 and IFN-γ, and positively correlated with IL-4. In Hashimoto's thyroiditis tissues, the expression of mTOR was higher while the expression of LC3B-II was lower than that of normal thyroid tissue. With the increase in 25-(OH)D3 concentration, the expression level of mTOR increased, the expression level of LC3B-II decreased and the apoptosis rate was significantly increased. The cell proliferation rate decreased with the increase in 25-(OH)D3 concentration. The serum 25-(OH)D3 level in HT hypothyroidism patients was significantly lower than that of the control group. Thus, 25-(OH)D3 may be involved in the disease progression by upregulating the levels of Th1 cytokines and downregulating the levels of Th2 cytokines. 25-(OH)D3 can inhibit autophagy of thyroid cells, induce apoptosis and participate in the pathogenesis of Hashimoto's thyroiditis.

In the Basis of Hashimoto’s Thyroiditis, to Form Papillary Thyroid Carcinoma, Metastasized and Then to De-Differentiate into Poorly Differentiated Squamous Cell Carcinoma

Thyroid squamous cell carcinoma is very rare. At present, it is limited to case reports. Since the thyroid follicular epithelium is the non-squamous epithelium, how primary squamous cell carcinoma (SCC) of the thyroid occurs is still a controversial issue. Hashimoto’s thyroiditis (HT) is considered to be an independent risk factor for thyroid cancer, under the basis of HT, how tumor cells evolve and develop to papillary thyroid carcinoma (PTC), and particularly to de-differentiate into SCC is elusive. We report a 72-year-old female patient who developed multiple subtypes of PTC on a basis of HT, and finally to de-differentiate into SCC within the local foci of lymph node metastasis. We found that there was a variety of sub-types of PTC in this patient in the background of HT. SCC was found within local lymph node metastasis. Pathomorphology, immunohistochemistry, and molecular pathology have confirmed that the SCC was derived from PTC, and then developed into poorly differentiated SCC and/or anaplastic carcinoma. We also conducted a comprehensive literature review.

Role of miR‐155‐5p expression and its involvement in apoptosis‐related factors in thyroid follicular carcinoma

Thyroid follicular carcinoma is a malignant tumor from thyroid follicular epithelium, which is prone to involve capsular and vascular invasion. The present study was conducted in order to detect the expression of microRNA-155-5p (miR-155-5p) in thyroid follicular carcinoma with an attempt to analyze its involvement in apoptosis-related factors. Forty-five patients with thyroid follicular carcinoma made up the observation group and 45 patients with thyroid follicular adenoma were included into the control group. Tissues of thyroid follicular carcinoma and thyroid follicular adenoma were obtained from the patients, and analysed for expression of miR-155-5p by real-time fluorescence quantitative PCR (qPCR). The expression of cysteine-containing aspartic acid protein hydrolase-3 (Caspase-3) in thyroid follicular carcinoma was detected with the use of Western Blot analyses. Immunohistochemical method was used to detect the expression of B-cell lymphoma protein-2 (Bcl-2) in thyroid follicular carcinoma. There was significant difference in the expression of miR-155-5p between the two groups (Observation vs Control: 1.46±0.42 vs 0.98±0.33 P<.05). The expression of miR-155-5p was significantly different in the maximum diameter of tumor, vascular invasion and neural invasion (maximum diameter of tumor <4cm vs ≥4cm: 1.36±0.40 vs 1.68±0.32, vascular invasion N vs Y: 1.35±0.42 vs 1.69±0.39, Neural invasion N vs Y: 1.35±0.38 vs 1.70±0.31 P<.05). However, there was no significant difference in the expression of miR-155-5p in terms of different gender, age and group with or without lymph node metastasis (P>.05). Based on survival analysis, patients with high expression of miR-155-5p experienced short survival time (median survival time was 45months, P<.05). There was a negative correlation between miR-155-5p and Caspase-3 (r=-.50, P<.05). In addition, positive correlation was observed between miR-155-5p and Bcl-2 (r=.55, P<.05). There was increased expression of miR-155-5p in thyroid follicular carcinoma. The abnormal expression of miR-155-5p may be an independent prognostic factor for thyroid follicular carcinoma associated with cell apoptosis.

Oncogenic pseudogene DUXAP10 knockdown suppresses proliferation and invasion and induces apoptosis of papillary thyroid carcinoma cells by inhibition of Akt/mTOR pathway.

Pseudogenes, another novel group of non-coding segments without protein-coding capacity, are closely associated with tumourigenesis and cancer progression. Double homeoboxA pseudogene 10 (DUXAP10) is reported to be robustly expressed in thyroid carcinoma. However, the functional role and underlying mechanism of DUXAP10 in papillary thyroid carcinoma (PTC) progression remain undefined. DUXAP10 expression in PTC cells was detected by qRT-PCR. Cell proliferation and invasion were determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell invasion assay, respectively. Apoptosis was evaluated using flow cytometry. Protein expression of matrix metalloproteinase (MMP)-2, MMP-9, protein kinase B (Akt), phosphorylated Akt, mammalian target of rapamycin (mTOR), and phosphorylated mTOR was examined by western blot. Results showed that DUXAP10 was significantly overexpressed in PTC cells compared with normal thyroid follicular epithelium cells. DUXAP10 silencing suppressed cell proliferation and invasive ability, reduced the expression of MMP-2 and MMP-9, and increased apoptotic rate and caspase-3 activity in PTC cells. Additionally, the Akt/mTOR pathway was inhibited following DUXAP10 knockdown in PTC cells. Activation of the Akt/mTOR pathway by 740Y-P and MHY1485 attenuated DUXAP10 knockdown-induced proliferation reduction, invasion suppression and apoptosis in PTC cells. In conclusion, DUXAP10 knockdown suppressed proliferation and invasion and induced apoptosis in PTC cells at least partially by inhibition of the Akt/mTOR pathway.

PTPN11 Knockdown Prevents Changes in the Expression of Genes Controlling Cell Cycle, Chemotherapy Resistance, and Oncogene-Induced Senescence in Human Thyroid Cells Overexpressing BRAF V600E Oncogenic Protein.

The MAPK (RAS/BRAF/MEK/ERK) signaling pathway is a kinase cascade involved in the regulation of cell proliferation, differentiation, and survival in response to external stimuli. The V600E mutation in the BRAF gene has been detected in various tumors, resulting in a 500-fold increase in BRAF kinase activity. However, monotherapy with selective BRAF V600E inhibitors often leads to reactivation of MAPK signaling cascade and emergence of drug resistance. Therefore, new targets are being developed for the inhibition of components of the aberrantly activated cascade. It was recently discovered that resistance to BRAF V600E inhibitors may be associated with the activity of the tyrosine phosphatase SHP-2 encoded by the PTPN11 gene. In this paper, we analyzed transcriptional effects of PTPN11 gene knockdown and selective suppression of BRAF V600E in a model of thyroid follicular epithelium. We found that the siRNA-mediated knockdown of PTPN11 after vemurafenib treatment prevented an increase in the expression CCNA1 and NOTCH4 genes involved in the formation of drug resistance of tumors. On the other hand, downregulation of PTPN11 expression blocked the transcriptional activation of genes (p21, p15, p16, RB1, and IGFBP7) involved in cell cycle regulation and oncogene-induced senescence in response to BRAF V600E expression. Therefore, it can be assumed that SHP-2 participates not only in emergence of drug resistance in cancer cells, but also in oncogene-induced cell senescence.

Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis

With the increasing incidence of papillary thyroid cancer (PTC), more attention has been paid to exploring the mechanism of PTC initiation and progression. In addition, ectopic expression of long noncoding RNAs (lncRNAs) is reported to play a pivotal role in multiple human cancers. Based on these findings, we examined lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) expression and its clinical significance, biological function and mechanism in PTC. First, we analyzed thyroid ABHD11-AS1 expression in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then, qRT-PCR was applied to detect the expression in paired PTC tissues and adjacent normal tissues, as well as in PTC cell lines (TPC-1 and K-1) and a normal thyroid follicular epithelium cell line (Nthy-ori3-1). In addition, we validated the relationship between ABHD11-AS1 expression and clinicopathological features by the Pearson X2 test. The oncogenic role of ABHD11-AS1 and its regulation of miR-199a-5p in PTC were examined by biological assays. Finally, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. We found that ABHD11-AS1 was remarkably overexpressed in PTC, and high expression was related to tumor size, lymph node metastasis, extrathyroidal extension and advanced TNM stage. Moreover, ABHD11-AS1 enhanced the abilities of cell proliferation, migration, and invasion, inhibited apoptosis in vitro, promoted tumorigenesis in vivo via sponging miR-199a-5p and then induced SLC1A5 activation. In addition, rescue assays were performed to confirm the ABHD11-AS1/miR-199a-5p/SLC1A5 axis. Taken together, the data show that ABHD11-AS1 acts as a competing endogenous RNA (ceRNA) to exert malignant properties in PTC through the miR-199a-5p/SLC1A5 axis. Therefore, our study may shed light on PTC diagnosis and therapies.

Influence of nonylphenol exposure on basic growth, development, and thyroid tissue structure in F1 male rats

ObjectiveEnvironmental endocrine disruptors (EEDs) with a weak ability to mimic estrogen have been associated with thyroid dysfunction. However, little is known about the effect of nonylphenol (NP), a well-known EED, on thyroid structure. The present study evaluates whether gestational and lactational exposure to NP impacts growth and thyroid structure in F1 male rats.MethodsA total of 60 rats were gavaged with NP (25, 50, and 100 mg/kg), estradiol (E2, 30 μg/kg/day), and corn oil alone (vehicle control) from gestational day 6 to postnatal day (PND) 21. Serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone levels were detected by automated chemiluminescence immunoassay analyzer. The NP level in the thyroid was measured using high-performance liquid chromatography. The ultrastructure of follicular epithelial cells was examined using transmission electron microscopy. Histopathology was conducted using hematoxylin and eosin staining.ResultsOn PND 0, exposure to 50 and 100 mg/kg/day NP led to a significant decrease in the average litter size, litter weight and number of live pups per litter compared to the control group (P < 0.05). Dams exposed to NP during perinatal period demonstrated decreased serum levels of FT3 and FT4 in F1 male rats, when compared to the control group (P < 0.05). The NP level in the control group was 3.39 ± 0.08 ng/mg, while NP levels in the low, middle, and high dose groups ranged from 5.20 to 11.00 ng/mg. Exposure caused a dose-related increase in NP level in the thyroid of male pups (P < 0.01). The thicknesses of the thyroid follicular epithelium were 2.06 ± 0.37 μm in the control group and 3.97 ± 1.61 μm in the high-dose group. The thickness of the thyroid follicular epithelium increased with an increase in treatment dose in a dose-dependent manner (P < 0.05). The sizes of the thyroid follicles were 1,405.53 ± 866.62 μm2 in the control group and 317.49 ± 231.15 μm2 in the high-dose group. With increasing NP dosages, animals showed a decreased size of the thyroid follicle (P < 0.01). Thyroid follicular cells of NP-treated rats showed mildly swollen mitochondria and dilated rough endoplasmic reticulum in the cytoplasm.ConclusionNonylphenol can cross the placental barrier and accumulate in the thyroid of F1 male rats. Gestational and lactational exposure to NP in dams impacted both development and growth of pups and damaged the ultrastructure of their thyroid tissue, which may further negatively influence normal thyroid function.

Extensive squamous metaplasia in papillary carcinoma of the thyroid: A potential diagnostic pitfall

It is a rare event to find squamous cells in the thyroid gland. Squamous metaplasia (SM) of the thyroid follicular epithelium is one of such conditions. SM can occur in association with nonneoplastic as well as neoplastic thyroid lesions. Here, we report a case of papillary carcinoma of the thyroid in a 26-year-old female showing extensive SM. On immunohistochemistry, squamous as well as papillary carcinoma component expresses CK7 and thyroglobulin. High molecular weight cytokeratin and p63 were positive in only in the squamous area, while TTF-1 was negative in these cells. Extensive SM in the thyroid can be misinterpreted as primary or metastatic squamous cell carcinoma. Further, the tumor may be mislabeled as collision tumors of thyroid. As it might lead to therapeutic implications, the distinction of SM in thyroid is necessary.

Papillary Thyroid Carcinoma Emerging from Hashimoto Thyroiditis Demonstrates Increased PD-L1 Expression, Which Persists with Metastasis.

There is evidence that programmed death-ligand 1 (PD-L1) is expressed by thyroid follicular epithelium in thyroiditis, but the role of PD-L1 in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to determine whether (1) the presence of background chronic lymphocytic thyroiditis (CLT) or Hashimoto thyroiditis (HT) influenced the expression of PD-L1 in benign follicular epithelium or in PTC and (2) if PD-L1 expression in PTC persisted with lymph node metastasis. We performed immunohistochemistry (IHC) for PD-L1 on formalin-fixed paraffin-embedded tissues. We first studied five cases of unremarkable thyroid, five cases of CLT, and five cases of HT without carcinoma. We subsequently performed PD-L1 IHC on ten cases of PTC arising in normal thyroid, ten cases of PTC arising in CLT, and ten cases of PTC arising in HT. Whenever available, we evaluated corresponding synchronous lymph node metastases from all cases for PD-L1 expression. PD-L1 expression was increased (10-90%) in all five cases of HT, only minimal expressed (1-5%) in two of five cases of CLT, and not expressed in five cases of unremarkable thyroid. PTC arising in normal thyroid or CLT nearly uniformly lacked PD-L1 expression. In contrast, PTC arising in HT demonstrated significant PD-L1 expression, which persisted in corresponding lymph node metastases. Background non-neoplastic follicular epithelium in the HT cases also demonstrated PD-L1 expression. Thyroid follicular epithelium in HT demonstrates increased PD-L1 expression, and PTC arising in a background of HT shows increased PD-L1 expression, which is retained with metastasis.

Jinlida Granules Improve Dysfunction of Hypothalamic-Pituitary-Thyroid Axis in Diabetic Rats Induced by STZ.

Objective We aim to explore the effects and mechanisms of Jinlida granules on the dysfunction of hypothalamic-pituitary-thyroid (HPT) axis in diabetic rats induced by streptozotocin. Methods A total of 48 SD rats were randomized into normal control group (NC, n = 6) and diabetic group (n = 42). Rats in diabetic group were randomly divided into diabetes mellitus (DM) control group, low, medium, and high doses of Jinlida group (JL, JM, and JH), medium dose of Jinlida plus Tongxinluo group (JM + T), metformin group (Met), and Saxagliptin group (Sax) (n = 6 in each group). Diabetic rats were obtained by intraperitoneal injection of streptozotocin and sacrificed at 8 weeks to examine the function of HPT axis. Results Levels of fasting blood glucose (P < 0.05), pIκB, TNFα (P < 0.05), pNF-κB, and IL-6 (P < 0.01) in liver tissue and TSHR mRNA expression (P < 0.01) in diabetic group were significantly increased, while levels of serum T3 and T4, thyroid hormone receptor (TR) mRNA and Dio1 mRNA in liver tissue, and sodium iodide symporter (NIS) mRNA in thyroid tissue in diabetic group were significantly decreased compared with those in NC group (P < 0.01). Among diabetic groups, level of fasting blood glucose in JH, JM + T and Met group was lower (P < 0.05) compared with DM group. However, levels of serum T3 and T4, TR mRNA in liver tissue, TSHR, and NIS mRNA in thyroid tissue in JH, JM + T, Met, and Sax group were significantly increased (P < 0.01) compared to DM group. In contrast, levels of Dio1 mRNA, pI-κB in Met and JM + T groups, pNF-κB in JH, JM + T, and Met group, and TNFα and IL-6 in JM, JH, JM + T, and Met group were significantly decreased (P < 0.05). HE staining showed reduced thyroid follicular epithelium and follicular area, as well as increased colloid area in DM group, indicating impaired synthesis, reabsorption, and secretory of TH in diabetes, which was significantly improved in JH, JM + T, and Met groups. Conclusion HPT axis dysfunction in DM could be significantly improved by Jinlida granules. The mechanism might be associated with the anti-inflammatory effects involving NF-κB pathway. Our findings suggested the potential benefit of Jinlida granules for patients with HPT axis dysfunction and DM, which was to be verified by more experimental and clinical studies.

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30mgkg-1 b.w. genistein (Orx+G) subcutaneously (s.c.) every day for 3weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P<0.05), but trabecular separation (Tb.Sp) was decreased (P<0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P<0.05) compared with Orx, whereas Vv of the colloid was lower (P<0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P<0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.

Sex Differences in the Production of SLC5A5, Thyroid Peroxidase, and Thyroid Hormones in Pubertal Rats Exposed to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) during Postnatal Ontogeny.

Sex differences in the expression of iodide transporter SLC5A5 and thyroid peroxidase in thyroid follicular epithelium and thyroid serum profile were assessed in pubertal rats exposed to endocrine disruptor DDT starting from the first postnatal day. It was found that exposure to DDT reduced expression of SLC5A5 in peripheral regions of thyroid lobes in males and in central regions in females. The most pronounced sex differences were observed in thyroid peroxidase expression that remained sensitive to thyroid stimulating hormone regulation in males and lost sensitivity to pituitary stimulation in females after exposure to disruptor, which determines more pronounced hypothyroidism in females.

Growth performance, morphometric analysis of the intestinal mucosa and thyroid of broiler fed canola meal

ABSTRACT The aim of this study was to evaluate the effect of replacing soybean meal with canola meal in broiler diets on performance, liver histopathology, morphometry of the intestinal mucosa and thyroid. One-day-old Cobb chicks (n=300) were distributed in a completely randomized design, with increasing levels of replacement of soybean meal with canola meal (0, 25, 50, 75 and 100%) and 6 repetitions of 10 birds each. Weight gain decreased linearly (P&lt; 0.05) with increasing levels of inclusion of canola meal, in all stages. Villus height in the duodenum and jejunum linearly decreased (P&lt; 0.05). Follicle diameter and thyroid follicular epithelium height increased linearly with increasing levels of canola meal (P&lt; 0.05). Similarly, there was an increase in relative weight of liver and heart, and liver steatosis in the highest levels of replacement. In conclusion, the replacement of soybean meal with canola meal can reduce performance, adversely affecting the thyroid, liver and the morphometric characteristics in the duodenum and jejunum.