Presence and distribution of urocortin and corticotrophin-releasing hormone receptors in the bovine thyroid gland

Urocortin (UCN), a 40 amino acid peptide is a Corticotrophin-Releasing Hormone (CRH) related peptide. The biological actions of CRH family peptides are mediated via two types of G-protein coupled receptors, CRH type 1 (CRHR1) and CRH type 2 (CRHR2). The aim of the present study was to investigate the expression of UCN, CRHR1 and CRHR2 by immunoprecipitation, Western blot, immunohistochemistry and RT-PCR in the bovine thyroid gland. Immunoprecipitation and Western blot analysis showed that tissue extracts reacted with the anti-UCN, -CRHR1 and –CRHR2 antibodies. RT-PCR experiments demonstrated that mRNAs of UCN, CRHR1 and CRHR2 were expressed. UCN-immunoreactivity (IR) and CRHR2–IR were found in the thyroid follicular and parafollicular cells and CRHR1-IR in the smooth muscle of the blood vessels. These results suggest that a regulatory system exists in the bovine thyroid gland based on UCN, CRHR1 and CRHR2 and that UCN plays a role in the regulation of thyroid physiological functions through an autocrine/paracrine mechanis

Nulliparity enhances the risk of second primary malignancy of the breast in a cohort of women treated for thyroid cancer

<p>Abstract</p> <p>Background</p> <p>Many studies have reported an increased risk of developing a second primary malignancy (SPM) of the breast in women treated for thyroid cancer. In this study, we investigated several potential risk factors for this association. The aim of this retrospective cohort study was to identify a subgroup of women surgically treated for papillary thyroid cancer that may benefit from more careful breast cancer screening.</p> <p>Methods</p> <p>A total of 101 women surgically treated for papillary thyroid cancer from 1996 to 2009 with subsequent follow-up were interviewed by phone regarding personal risk factors and lifestyle habits. Only 75 questionnaires could be evaluated due to a 25.7% rate of patients not retrieved or refusing the interview. Data analysis was performed using a multivariate logistic model.</p> <p>Results</p> <p>The standardised incidence ratio (SIR) for breast cancer was 3.58 (95% IC 1.14 - 8.37). Our data suggest a protective effect of multiparity on the development of a SPM of the breast (O.R. 0.15; 95% IC 0.25 - 0.86). Significant associations were not found with other known risk factors including Body Mass Index (BMI), age at first tumour, concurrent metabolic diseases, smoking, physical activity and familiarity.</p> <p>Conclusions</p> <p>This study confirms that a higher incidence of SPM of the breast is observed in women treated for papillary thyroid cancer. Additionally, this risk is increased by nulliparity, thus a strict breast screening program for nulliparous women treated for thyroid cancer may be advisable.</p

The interaction of chemicals isolated from municipal wastewater effluent with rainbow trout (Oncorhynchus mykiss) thyroid hormone receptors

The normal function of the thyroid hormone (TH) system is essential for growth, development and metabolism in humans as well as in other species. The action of TH is dependent on its binding to thyroid hormone receptors (THR) found in the cell nucleus. In some situations, chemicals with structural similarities to TH can bind to these receptors and disrupt their normal function. It has been previously demonstrated that environmental contaminants including, carbamazapine, nonlyphenol (NP), bisphenol A (BPA), and several others are able to bind to the THR as either agonists or antagonists and modulate downstream biochemical responses. Municipal wastewater effluent (MWWE) is a major source of these contaminants entering aquatic environments. Recently extracts of MWWE have been shown to contain chemicals that are capable of binding to THRs. However, MWWE is a complex mixture of chemicals and the specific chemicals have not been identified. In this thesis, a proof of concept was developed for using an Effects Directed Assessment (EDA) approach to isolate thyroid receptor active compounds in MWWE. An EDA is a technique created to extract and identify chemicals from complex mixtures, using various fractionation methods. Once these chemicals have been identified, they are further reviewed for biological relevance. A competitive binding assay for THR was developed and applied to determine the relative binding affinity of known environmental contaminants to THR. Nuclear thyroid hormone receptors were isolated from rainbow trout liver by differential centrifugation. This method involved liver tissue homogenization and subsequent centrifugations to separate the nuclear fraction containing the receptors. The binding characteristics of the isolated THR were evaluated using the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in a competitive binding assay. Minimal binding affinity was present in this assay and future studies should validate the assay further and assure that it is comparable to literature values. Environmental contaminants, including BPA, NP were also tested to determine their relative binding affinity to the THRs compared to the endogenous hormones. High concentrations of both BPA and NP bound to the thyroid hormone receptor, displacing radiolabeled T3 from its binding site. The rainbow trout competitive binding assay was also used to test the binding affinities of extracts from two municipal wastewater effluents collected in the Grand River watershed in southern Ontario. Effluents were extracted using a solid phase adsorbent (HLB Oasis cartridge), eluted with methanol, taken to dryness then reconstituted in ethanol for use in the assay. Both effluent extracts displaced the binding of radiolabeled T3 to the thyroid receptors. The studies demonstrate that a competitive THR assay can be used to detect chemicals in complex mixtures with the potential to interact with THRs. The next step should be to apply the assay using an EDA approach to isolate and identify specific chemicals in effluents that are not yet known to bind to the THR. Interference with the normal function of the TH system has the potential to disrupt normal growth, development and metabolism in aquatic organisms in the receiving environments

Draft toxicological profile for iodine

Draft for public comment.Comment period ends: February 22, 2002.Prepared by: Syracuse Research Corporation under contract no. 205-1999-00024; prepared for: U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry205-1999-0002

Toxicological profile for iodine

prepared by Syracuse Research Corporation under contract no. 205-1999-00024 ; prepared for U.S. Dept. of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry."April 2004.""A Toxicological Profile for Iodine, Draft for Public Comment was released in September 2001. This edition supercedes any previously released draft or final profile."--P. iii.Chemical manager(s)/author(s): John Rishe ... [et al.].Also available via the World Wide Web.Includes bibliographical references (p. 325-495)