No description available.

No description available.

The role of selected hormones in the control of hair follicle activity, fibre growth and moult in cashmere goats was investigated by manipulation of prolactin (PRL), thyroid hormones, and growth hormone (GH) individually or in combination. In experiment 1, the effect of different doses of the anti-thyroid drug "propylthiouracil" (PTU), on thyroxine (T4) and triiodothyronine (T3) profiles and deiodinase enzyme activities in liver, kidney and skin tissues was determined. Types II and III deiodinase enzymes were found to be present in goat skin but not type I. It was concluded that the supply of T3 within the skin was partly independent of circulating hormone profiles. In experiment 2, goats were treated with PTU, triiodothyronine (T3) and bromocriptine (Br) to decrease T3 availability to tissues and circulating PRL concentrations, respectively. Treatment with Br delayed the spring rise in plasma PRL concentrations (P=0.06) and primary (P<0.05) hair follicle activity, and delayed moult onset (P<0.01). PTU treatment did not significantly affect hair follicle activity but generally delayed the time of moult onset (P<0.05). The effects of the treatments were not additive, indicating that the actions of the two hormones were not independent. The effects of PTU and Br treatments were not exerted through changes in IGF-I binding activity in the skin, but binding was greater (P<0.01) in April than November. In experiment 3, treatment with bovine somatotropin (bST), T4 or metoclopramide to increase circulating concentrations of GH, T4 or PRL, failed to prolong the period of anagen in hair follicles, but bST increased fibre growth rate (P<0.05) and this was associated with higher circulating IGF-I concentrations. It is concluded that manipulation of the cycle of the cashmere-producing hair follicle is unlikely to be achieved through manipulation of circulating hormone concentrations alone and that much regulation of hair follicle activity occurs within the skin itself, possibly through changes in enzymes that control the supply of T3 to the follicles, in hormone receptor activity, and in the rate of synthesis of IGF-I and other growth factors within the skin.

<p>Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) that have been heavily used in consumer products such as furniture foams, plastics, and textiles since the mid-1970’s. BFRs are added to products in order to meet state flammability standards intended to increase indoor safety in the event of a fire. The three commercial PBDE mixtures, Penta-, Octa-, and DecaBDE, have all been banned in the United States, however, limited use of DecaBDE is still permitted. PBDEs were phased out of production and added to the Stockholm Convention due to concerns over their environmental persistence and toxicity. Human exposure to PBDEs occurs primarily through the inadvertent ingestion of contaminated house dust, as well as though dietary sources. Despite the phase-out and discontinued use of PBDEs, human exposure to this class of chemicals is likely to continue for decades due to the continued use of treated products and existing environmental reservoirs of PBDEs. Extensive research over the years has shown that PBDEs disrupt thyroid hormone (TH) levels and neurodevelopmental endpoints in rodent and fish models. Additionally, there is growing epidemiological evidence linking PBDE exposure in humans to altered TH homeostasis and neurodevelopmental impairments in children. Due to the importance of THs throughout gestation, there is a great need to understand the effects of BFRs on the developing fetus. Specifically, the placenta plays a critical role in the transport, metabolism, and delivery of THs to the fetal compartment during pregnancy and is a likely target for BFR bioaccumulation and endocrine disruption. The central hypothesis of this dissertation research is that BFRs disrupt the activity of TH sulfotransferase (SULT) enzymes, thereby altering TH concentrations in the placenta.</p><p>In the first aim of this dissertation research, the concentrations of PBDEs and 2,4,6-TBP were measured in a cohort of 102 placenta tissue samples from an ongoing pregnancy cohort in Durham, NC. Methods were developed for the extraction and analysis of the BFR analytes. It was found that 2,4,6-TBP was significantly correlated with all PBDE analytes, indicating that 2,4,6-TBP may share common product applications with PBDEs or that 2,4,6-TBP is a metabolite of PBDE compounds. Additionally, this was the first study to measure 2,4,6-TBP in human placenta tissues.</p><p>In the second aim of this dissertation research, the placenta tissue concentrations of THs, as well as the endogenous activity of deiodinase (DI) and TH SULT enzymes were quantified using the same cohort of 102 placenta tissue samples. Enzyme activity was detected in all samples and this was the first study to measure TH DI and SULT activity in human placenta tissues. Enzyme activities and TH concentrations were compared with BFR concentrations measured in Aim 1. There were few statistically significant associations observed for the combined data, however, upon stratifying the data set based on infant sex, additional significant associations were observed. For example, among males, those with the highest concentrations of BDE-99 in placenta had T3 levels 0.80 times those with the lowest concentration of BDE-99 (95% confidence interval (CI): 0.59, 1.07). Whereas females with the highest concentrations of BDE-99 in placenta had T3 levels 1.50 times those with the lowest concentration of BDE-99 (95% CI: 1.10, 2.04). Additionally, all BFR analyte concentrations were higher in the placenta of males versus females and they were significantly higher for 2,4,6-TBP and BDE-209. 3,3’-T2 SULT activity was significantly higher in female placenta tissues, while type 3 DI activity was significantly higher in male placenta tissues. This research is the first to show sex-specific differences in the bioaccumulation of BFRs in human placenta tissue, as well as differences in TH concentrations and endogenous DI and SULT activity. The underlying mechanisms of these observed sex differences warrant further investigation. </p><p>In the third aim of this dissertation research, the effects of BFRs were examined in a human choriocarcinoma placenta cell line, BeWo. Michaelis-Menten parameters and inhibition curves were calculated for 2,4,6-TBP, 3-OH BDE-47, and 6-OH BDE-47. 2,4,6-TBP was shown to be the most potent inhibitor of 3,3’-T2 SULT activity with a calculated IC50 value of 11.6 nM. It was also shown that 2,4,6-TBP and 3-OH BDE-47 exhibit mixed inhibition of 3,3’-T2 sulfation in BeWo cell homogenates. Next, a series of cell culture exposure experiments were performed using 1, 6, 12, and 24 hour exposure durations. Once again, 2,4,6-TBP was shown to be the most potent inhibitor of basal 3,3’-T2 SULT activity by significantly decreasing activity at the high and medium dose (1 M and 0.5 M, respectively) at all measured time points. Interestingly, BDE-99 was also shown to inhibit basal 3,3’-T2 SULT activity in BeWo cells following the 24 hour exposure, despite exhibiting no inhibitory effects in the BeWo cell homogenate experiments. This indicates that BDE-99 must act through a pathway other than direct enzyme inhibition. Following exposures, the TH concentrations in the cell culture growth media and mRNA expression of TH-related genes were also examined. There was no observed effect of BFR treatment on these endpoints. Future work should focus on determining the downstream biological effects of TH SULT disruption in placental cells, as well as the underlying mechanisms of action responsible for reductions in basal TH SULT activity following BFR exposure. </p><p>This was one of the first studies to measure BFRs in a cohort of placenta tissue samples from the United States and the first study to measure THs, DI activity, and SULT activity in human placenta tissues. This research provides a novel contribution to our growing understanding of the effects of BFRs on TH homeostasis within the human placenta, and provides further evidence for sex-specific differences within this important organ. Future research should continue to investigate the effects of environmental contaminants on TH homeostasis within the placenta, as this represents the most critical and vulnerable stage of human development.</p> / Dissertation

No abstract in the thesis

Lee Mei Lan May. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 48-56). / Abstracts in English and Chinese. / ABSTRACT --- p.I / 中文摘要 --- p.III / ACKNOWLEDGEMENTS --- p.IV / PUBLICATION --- p.V / LIST OF FIGURES --- p.VI / LIST OF TABLES --- p.VII / ABBREVIATION --- p.VIII / CONTENTS --- p.IX / Chapter CHAPTER ONE: --- INTRODUCTION AND LITERATURE / Chapter 1.1 --- THYROID CANCER AND ITS EPIDEMIOLOGY --- p.1 / Chapter 1.1.1 --- Histology --- p.1 / Chapter 1.1.2 --- Gender comparison --- p.3 / Chapter 1.1.3 --- Female hormone 一 risk factor --- p.6 / Chapter 1.2 --- BIOLOGICAL BACKGROUND OF HORMONE´-´ؤؤ --- p.7 / Chapter 1.2.1 --- Estrogen --- p.8 / Chapter 1.2.2 --- Estrogen antagonist --- p.9 / Chapter 1.2.3 --- Estrogen receptors --- p.10 / Chapter 1.2.4 --- Estrogen receptor and thyroid cancer --- p.12 / Chapter 1.3 --- THE ROLE OF APOPTOSIS --- p.13 / Chapter 1.3.1 --- Bcl-family protein --- p.13 / Chapter 1.3.2 --- Bcl-family protein and cancer --- p.14 / Chapter 1.3.3 --- Estrogen and Bcl-family protein --- p.15 / Chapter 1.4 --- Objectives --- p.16 / Chapter CHAPTER TWO: --- GENERAL MATERIALS AND METHODS / Chapter 2.1 --- MATERIALS --- p.17 / Chapter 2.1.1 --- Culture media and treatment reagents --- p.17 / Chapter 2.1.2 --- Reagents for Western blot assay --- p.18 / Chapter 2.1.3 --- Antibodies --- p.19 / Chapter 2.1.4 --- Materials for RT-PCR --- p.19 / Chapter 2.1.5 --- Kits --- p.20 / Chapter 2.1.6 --- Instrumentations --- p.20 / Chapter 2.2 --- Methods --- p.21 / Chapter 2.2.1 --- Cell culture and treatment --- p.21 / Chapter 2.2.2 --- MTT assay --- p.22 / Chapter 2.2.3 --- Western blot analysis --- p.23 / Chapter 2.2.3.1 --- Protein extraction --- p.23 / Chapter 2.2.3.2 --- SDS-PAGE and protein transfer --- p.23 / Chapter 2.2.3.3 --- Immunoblotting analysis --- p.24 / Chapter 2.2.4 --- RNA extraction and RT-PCR --- p.25 / Chapter 2.2.4.1 --- RNA extraction --- p.25 / Chapter 2.2.4.2 --- cDNA synthesis --- p.26 / Chapter 2.2.4.3 --- Polymerase Chain Reaction (PCR) --- p.27 / Chapter 2.2.5 --- Statistical analysis --- p.28 / Chapter CHAPTER THREE: --- RESULTS / Chapter 3.1 --- Effect of E2 and tamoxifen on proliferation --- p.29 / Chapter 3.2 --- Comparison of effects of E and testosterone on Proliferation --- p.31 / Chapter 3.3 --- Differential Bcl-xL expression in response to E2 and testosterone stimulation --- p.33 / Chapter 3.4 --- Expression of ERα and ERβ in response to E2 stimulation --- p.35 / Chapter 3.5 --- Bcl-xL and Bax protein expression in response to E2 stimulation --- p.36 / Chapter 3.6 --- Expression of Bcl-xL and Bax mRNA in response to E2 stimulation --- p.39 / Chapter CHAPTER FOUR: --- DISCUSSION --- p.41 / Chapter CHAPTER FIVE: --- CONCLUSION --- p.47 / REFERENCES --- p.48

Ho Sin Yee, Stella. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 94-105). / Background --- p.1 / Chapter Chapter 1 --- Introduction / Thyrotoxicosis --- p.3 / Graves' Disease --- p.5 / Laboratory Assessment of the Mothers --- p.7 / Placental Transfer --- p.10 / Effects of Maternal Thyroid and Antithyroid Agents on the Fetus --- p.13 / Diagnostic and Screening Tests for Fetal Thyroid Dysfunction --- p.19 / Fetal Treatment --- p.21 / Aims and Objectives of the Research --- p.24 / Chapter Chapter 2 --- Subjects and Methods / Patients' Profile --- p.26 / Categorization of the Thyrotoxic Population --- p.28 / Intraobserver Error --- p.30 / Pilot Study --- p.31 / Equipment --- p.31 / Measurements --- p.32 / Growth Charts employed --- p.32 / Imaging Technique --- p.33 / Calculations --- p.39 / Gestational Age of the Fetus --- p.41 / Analytical Methods --- p.43 / Chapter Chapter 3 --- Results / Intraobserver Error --- p.45 / Pilot Study --- p.45 / Maternal Thyroid Status (Thyrotoxic Population) --- p.48 / Fetal Thyroid Volume --- p.49 / Rate of Fetal Thyroid Growth --- p.59 / Fetal Thyroid Volume to Estimated Fetal Weight Ratios (V/W) --- p.60 / Birthweight of the Infants --- p.63 / Chapter Chapter 4 --- Discussion / Methodology --- p.64 / Findings and Observations --- p.71 / Chapter Chapter 5 --- Conclusions --- p.92 / References --- p.94 / Appendix I --- p.106

Orientador: Célia Regina Nogueira / Resumo: Os hormônios tireóideos, o estrógeno e outros hormônios atuam no crescimento e desenvolvimento do tecido mamário. Os receptores de estrógeno devem estar presentes para que o estrógeno possa atuar na atividade biológica das células mamárias. A presença ou ausência destes receptores no tecido tem influência direta na terapêutica e prognóstico clínico do câncer de mama. Os receptores do estrógeno e do hormônio tireóideo (T3) são membros da "superfamília de receptores" intracelulares. Estes receptores atuam na ativação da transcrição de genes alvo, através da união ao seu elemento responsivo hormonal. Ainda não se sabe de que forma o hormônio tireóideo atua no tecido tumoral mamário. Estudos epidemiológicos são contraditórios, mostrando que, quando os níveis de T3 estão elevados existe proteção contra o desenvolvimento de câncer de mama. Outros estudos demonstram haver aumento no risco e incidência do câncer mamário em pacientes hipertireoideas. Análises in vitro demonstraram que o T3, em concentrações suprafisiológicas induz a proliferação celular. Em pacientes com câncer de mama realizamos dosagens hormonais e verificamos a expressão dos receptores de estrógeno. Também foi estudada a conformação da molécula do T3 e do receptor de estrógeno, para confirmar se uma possível ligação estaria ocorrendo entre o T3 e o ER... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Thyroid hormones, estrogen and other hormones act in the growth and development of breast tissue. Estrogen receptors must be present so that estrogen can act in the biological activity of breast cells. The presence or the abscense of these receptors in tissue has direct influence on therapeutics and clinical prognostic of breast cancer. Estrogen and thyroid hormone (T3) receptors are members of intracellular "receptors superfamily". These receptors work in the activation of the transcription of target genes, linking them to their hormonal responsive. It is not known in which way thyroid hormone act in tumoral breast tissue. Epidemiologic studies are contradicting, showing that, when T3 levels are high, there is protection agains the development of breast cancer. Other studies show that there must be an increase in the risk and incidence of breast cancer in hyperthyroidean patients. In vitro analysis present that supra-physiologicals concentrations of T3 induces cellular proliferation. We performed hormonal dosage and verified the expression of estrogen receptors in breast cancer patients. The morphology of T3 molecule and of the estrogen receptor were also studied, to confirm if a possible link would exist between T3 and ER. Our results show an existance of a clinical relation between thyroid... (Complete abstract, click electronic access below) / Mestre

No description available.

Includes bibliographical references (leaves 191-207) / xiv, 207 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the interactions between thyroid hormones and male reproductive function in mature, prepubertal and post pubertal Merino rams. Hypothyroidism or hyperthyroidism was induced in these rams for 8-10 weeks and their reprodroductive endocrine axis and testis functions were assessed. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1986