Functional and morphological characterization of rat thyroid gland at remote periods following single high and low dose radiation exposure

A study of the morphological structure and functional activity of the rat thyroid gland was carried out after 22 months following a single exposure to external radiation. The 3-month-old animals were irradiated with doses of 0.25, 0.5, 1.0, 2.0 and 5.0 Gy. Blood was assayed for thyroxin (T4) and triiodothyronine (T3) levels, while liver tissue--for NADP-MDH activity and thyroid tissue--for thyroperoxidase activity. The thyroid was studied histologically, morphometrically and by electron microscope. The decreased T4 concentrations 2.59-fold in the 5.0 Gy group, the increased T3/T4 in the 2.0 and 0.25 Gy groups, the reduced diameter of cellular nuclei and follicles, the flat follicular epithelium and diminished number of thyrocyte ultrastructures indicate thyroid hypofunction in the irradiated animals. The morphological changes are characterized by enhanced diffuse and focal sclerotic changes in thyroid, most pronounced at high irradiation doses (1.0-5.0 Gy), whereas the hemosiderosis foci suggest that the structural changes are consequences of radiation-induced destructive injuries in the gland parenchyma. Two of the thyroids (0.5 Gy) demonstrate foci with pronounced lymphoid infiltration, while follicular carcinomas were detected in 4 thyroids (2.0 Gy), and in one thyroid (0.5 Gy) in one thyroid (5.0 Gy). The remote effects of radiation were dose-dependent destructive, sclerotic and atrophic processes, decreased functional activity, stimulation of development of autoimmune aggression and carcinogenesis in thyroid.     

Response of the developing thyroid gland of rats to a single gamma-irradiation in the period of intrauterine development

A single external exposure of pregnant rats to 2 Gy gamma-radiation caused changes in the functional status of the thyroid gland in offsprings at varying times of the postnatal development. The disturbance of the thyroid hormones balance in the blood, destruction of the thyroid gland combined with high functional tension of secretory elements, and activation of the thyrotropic function of hypophysis were revealed at remote times after irradiation.     

The effect of one-time external gamma irradiation at different stages of ontogeny on the thyroid status of rats]

A single external gamma-irradiation (1 Gy) of rats on day 35 of their life causes stable structural and functional disturbances in the thyroid gland leading to the development of hypothyrosis at the remote times following irradiation which is demonstrated by the decrease in the concentration of thyroxine in the blood, increase in the thyrotropic function of the hypophysis and inhibition of the activity of tyrosine-dependent enzyme, alpha-glycerophosphate dehydrogenase, in the liver. Disturbances induced by such exposure in the thyroid gland of adult rats are insignificant and compensatory in time.     

Fine structure of the fetal rat thyroid and parathyroid glands at term and during prolonged gestation

Summary The fine structure of the fetal rat thyroid and parathyroid glands was studied at term and during prolonged gestation, which was induced by subcutaneous injections of progesterone to the mothers from gestational days 20 through 24. At term, the follicular and parafollicular cells of the thyroid as well as cells of the parathyroid exhibited well developed cytoplasmic organelles. Morphological changes were not detected in either of the endocrine glands during prolonged gestation. The results are discussed in relationship to 1) thyroid follicular cell activity during stress and 2) the function of thyroid parafollicular and parathyroid cells in calcium homeostasis.Supported by the Medical Research Council of Canada Grant No. MA4740.     

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32

The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after gamma irradiation revealed that early-passage follicular cultures had significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures (0.11 Gy(-1)) (P < 0.0001, n = 12). As an additional way to determine whether connexin 32 was contributing to the difference in survival, cultures were treated with heptanol, resulting in higher alpha values, with early-passage cultures (0.10 Gy(-1)) nearly equivalent to untreated late-passage cultures (0.11 Gy(-1)) (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in gamma-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had alpha values that were not significantly different whether cells expressed functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)), or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower alpha values from the gamma-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the expression of connexin 32-type gap junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation was independent of their ability to communicate through connexin 32 gap junctions. (3) The fact that the beta components of the survival curves from both gamma rays and proton beams were similar (average 0.022 +/- 0.008 Gy(-2), P > 0.1, n = 39) suggests that at higher doses the loss of viability occurs at a relatively constant rate and is independent of radiation quality and the presence of functional gap junctions.     

Features of the development of the pituitary-thyroid system of the Wrangel Island hoofed lemming Dicrostonyx torquatus at stages of growth and peak population

By means of morphometric techniques, peculiarities in formation of the hypophyseal-thyroid system during prenatal and early postnatal periods have been studied in lemmings (Dicrostonyx torquatus) from the Wrangel island at growth stages and at the peak of the population quantity. Folliculoformation rate, time when the organ reaches the definitive structure, periods for establishing connection with the regulating center--the anterior hypophyseal lobe, correlation of differentiation rates of histo- and ultrastructures of the organ distinctly react to changes in the density population of the animals. Periods of initiation of folliculoformation are early and comparable at both stages of the population cycles. However, further at the peak of the population quantity, an essential retardation in the development of both histo- and ultrastructures of the thyroid cells is observed; formation of the histostructure significantly overtakes differentiation of the ultrastructures composing its cellular elements. The follicular structure begins to form only in newborn animals, the folliculogenesis completes on the 1st-6th days of the postnatal period. At the stage of growth of the population quantity, the folliculogenesis lasts 2 days (the 15th-17th days of the prenatal development), the organ's structure becomes definitive on the 17th day, at the same period connections are established with the anterior hypophyseal lobe. The role of the thyroid hormones in formation of reprodactive and adaptive potencies of the organism at various stages of the population cycle is discussed.     

Down regulation of hypertrophied follicular cell volume in thyroid hyperplastic gland

In the present study, changes in thyroid follicular cell volume and its regulation have been investigated during the early involution of a hyperplastic goitre. Male Wistar rats were administered an iodine deficient diet for 6 months with propylthiouracil (PTU, 0.15%) during the last two months. At the end of iodine deficiency (day 0), some rats were killed and the others received a normal iodine diet. These rats were killed after different periods of iodine refeeding. Thyroid follicular cell volume was very high in hyperplastic gland whereas thyroid protein concentration was low. Thyroid follicular cell volume quickly decreased when rats were normally iodine refed, whereas thyroid protein concentration increased. Electron microscopal observations showed that thyroid follicular cells retained their endocrine aspect in hyperplastic state and throughout the iodine refeeding period. Using concomitant stereological and biochemical techniques, it is shown that the amount of cellular iodide and an unknown iodinated compound strongly increased during the early iodine refeeding. Plasma TSH was high on day 0 and remained at this level until day 8 whereas plasma T3 and T4 were low on day 0 and remained at this low level until day 4. The present data show that the involution of thyroid follicular cell volume is induced by iodide and mediated by an iodinated compound at least in the initial phase, and is independent of plasma TSH, T3, T4, so indicating the involvement of a thyroid autoregulatory mechanism. These changes in cell volume may be of importance in ion transport, i.e. in the metabolism of thyroid follicular cell during the early involution of the hyperplastic goitre.     

Complex estimation of thyroid gland state in tundra voles, inhabiting the natural radioactive polluted sites

Behow is presented the complex state of thyroid gland of tundra voles living in high level natural radioactivity conditions (Ukhta region of Komi Republic) by morphological and functional criteria. High sensitivity of thyroid gland under natural chronic irradiation of whole organism is noticed. The essential changes in the morphological structure and in the hormone level of the thyroid gland are found in animals, which live for a long time in the conditions of the radioactive pollution. It is determined, that the inside population processes influence on the structure and on the funcition of the thyroid gland.     

Morphological changes in the human thyroid gland cultivated in continual flow system

In the present pilot study, the human thyroid gland tissue was cultivated under continuous culture conditions in the culture chambers of the ACUSYST-S system to determine morphological changes as well as the secretion of thyreoglobulin (Tgl) and thyroid hormones. After 24 hours of cultivation the follicular structure of the tissue was preserved in peripheral parts only, and there were regressive changes in the epithelium center. After 72 hours the regressive changes appeared in isolated follicles only; the size of the follicles increased, the height of the follicular epithelium decreased and there were macrophages present with phagocytized cell debris. After 144 hours disintegration of epithelia took place in the centre, while at the periphery the original follicles survived and very tiny new follicles formed, consisting of only 6 to 8 cells each and surrounding in section the homogeneous colloid. The parenchyma picture suggests a possibility of functional regeneration as an expression of adaptation to the conditions newly arisen during cultivation in a culture chamber. There was no significant influencing of the thyroid hormone secretion during cultivation. On the other hand, the Tgl secretion decreased throughout cultivation.     

Magnetic resonance imaging and spectroscopy of the rat hippocampus 1 month after exposure to 56Fe-particle radiation

The response of the central nervous system to space radiation is largely unknown. The hippocampus, which is known for its critical role in learning and memory, was evaluated for its response to heavy-ion radiation. At 1 month, animals exposed to brain-only 56Fe-particle irradiation (0-4 Gy) were examined using contrast-enhanced T1 imaging (CET1), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and (1)H-magnetic resonance spectroscopy (MRS). Correlative histology was performed after imaging. The T2WI, DWI and CET1 images revealed no overt anatomical changes after irradiation. Quantitative analysis demonstrated a significant increase in T2 at 2 Gy compared to 0 Gy. The apparent diffusion coefficient (ADC) revealed an inverse dose-dependent quantitative change in water mobility. Compared to 0 Gy, the ADC increased 122% at 1 Gy and declined to 44% above control levels at 4 Gy. MRS showed a significant increase in the N-acetylaspartate/choline ratio at 4 Gy and a lactate peak. Histology demonstrated no overt pathological changes in neuronal and astrocyte populations. However, a significant inverse dose-dependent morphological change in the microglial population was detected in irradiated animals. Our results suggest that early tissue matrix modifications induced by 56Fe-particle radiation can be detected by MRI in the absence of evident histopathology. These changes may indicate fundamental changes in the structure and function of the hippocampus.     

Ultrasound study in the differential diagnosis of thyroid focal lesions of various origin

The present study deals with the ultrasound differential diagnosis of thyroid lesions. A hundred and ninety-two patients, including 130 patients with benign diseases (nodular colloidal goiter) (36.9%), chronic autoimmune thyroiditis (30.7%), and adenomas (32.3%) and 62 patients with malignant diseases (thyroid cancer (88%), lymphoproliferative diseases (6.4%), and recurrent thyroid cancer) (4.8%), were clinically examined. Ultrasound studies (USS) were performed in the B- and (see text symbols) modes. The diagnosis was verified from cytological and histological findings with mandatory morphological confirmation. Interdisease comparison has shown that USS is both a screening and diagnostic technique in revealing thyroid changes and determining their site, sizes, and structure. Ultrasound pathognomonic signs were detected in different morphological types of adenomas, thyroiditis, and nodular colloidal goiter, in the classical, pseudoadenomatous and pseudocystic types of thyroid cancer. At the same time there were characteristic ultrasound parameters at the stage of pronounced changes in undifferentiated thyroid cancer (pseudothyroiditis), lymphoproliferative diseases, and acute thyroiditis. The exception was the diffuse form of chronic autoimmune thyroiditis in which both thyroid lobes were always altered.     

Interrelationships between pars intermedia and posterior pituitary with regard to corticotrophic and thyrotrophic partial function in rats

Functional interrelationships between the pars intermedia and posterior pituitary were proved under different experimental conditions. After stimulation of the thyrotropical axis of rats by an acute intraperitoneal application of 50 microgram TRH/rat the nuclear sizes of the thyroid follicular and the anterior pituitary thyrotropical cells increased according to a monophasic time curve with maximal amplitude at the time of 30 minutes. Interestingly, the nuclear sizes of the posterior pituitary cells were also enhanced. Under the same experimental conditions the nuclear areas of the cells of the external layer of the adrenal zona fasciculata decreased as did the nuclei of the pars intermedia cells (without regard to the cell type or localization of the cells in the intermediate lobe). Stimulation of the adrenocorticotropical axis by an acute injection of 0.2 ml isotonic saline solution/rat was followed by a time-dependent increase of nuclear sizes of the fasciculata cells and pars intermedia, whereas the nuclear volumes of the thyroid follicular cells, the anterior pituitary thyrotropical cells and the posterior pituitary cells decreased. Thus the functional state of the pars intermedia was in accordance with that of the adrenal cortex. Also the posterior pituitary cells responded to stimuli applied to the thyrotropical axis at the same degree as the thyrotropic organs themselves. Between the nuclear sizes of the pars intermedia and posterior pituitary we established the same inverse functional relationships as between the adrenal cortex and the thyroid gland.     

Morphological and functional changes in pituitary‐thyroid axis following prolonged exposure of female rats to constant light

Light regulates numerous physiological functions and synchronizes them with the environment, in part by adjusting secretion of different hormones. We hypothesized that constant light (CL) would disturb pituitary‐thyroid axis. Our aim was to determine morphological and functional changes in this endocrine system in such extreme conditions and, based on the obtained results, to propose the underlying mechanism(s). Starting from the thirtieth postnatal day, female Wistar rats were exposed to CL (600 lx) for the following 95 days. The controls were maintained under the regular laboratory lighting conditions. After decapitation, pituitaries and thyroids were prepared for further histomorphometric, immunohistochemical, and immunofluorescence examinations. Concentration of thyroid stimulating hormone (TSH), total T₄ and T₃ (TH) were determined. Thyroid tissue of light‐treated rats was characterized by microfollicular structure. We detected no change in total thyroid volume, localization and accumulation of thyroglobulin, thyroid peroxidase, and sodium‐iodide symporter in the follicular epithelium of CL rats. The volume of follicular epithelium and activation index were increased, while volume of the colloid and serum levels of TH decreased. In the pituitary, the relative intensity of TSH β‐immunofluorescence signal within the cytoplasm of thyrotrophs increased, but their average cell volume and the relative volume density decreased. Serum TSH was unaltered. We conclude that exposure of female rats to CL induced alterations in pituitary‐thyroid axis. Thyroid tissue was characterized by microfollicular structure. Serum TH levels were reduced without accompanying increase in serum TSH. We hypothesize that increased secretion and clearance of TH together with unchanged or even decreased hormonal synthesis, resulted in decreased serum TH levels in CL group. We assume this decrease consequently led to increased synthesis and/or accumulation of pituitary TSH. However, decreased average TSH cell volume and relative volume density, together with unchanged serum TSH, point to additional, negative regulation of thyrotrophs. J. Morphol. 275:1161–1172, 2014. © 2014 Wiley Periodicals, Inc.     

Differential radiation sensitivity to morphological, functional and molecular changes of human thyroid tissues and bone marrow cells maintained in SCID mice

Morphology and function of human organs and tissues are well maintained in the improved SCID (severe combined immunodeficient) mice for a long period (approximately 3 years). To study the radiation-induced damage on human thyroid gland, human thyroid tissues transplanted to SCID mice were consecutively exposed to X-rays or 137Cs gamma-rays at high and low dose rates for approximately 2 years. Consecutive irradiation resulted in the disappearance of follicles and significant decrease of thyroid hormone secretion. Mutations in p53 and c-kit genes were induced significantly in human thyroid tissues from old head and neck cancer patients (av. 56.8 years, 4 males) and a Graves' disease patient (20 years, male) over the dose of 24 Gy (44.7+/-5.9 Gy, mean+/-S.E) and 11 Gy (20.2+/-7.8 Gy), respectively, while mutations were not detected at lower doses nor in unexposed matched controls (p < 0.01). There were significant differences in mutation frequency in the transplanted human thyroid tissues (31 years, female) between high dose rate (1.19 Gy/min; 8 in 20 tissues) and low dose rate (0.00023 Gy/min; 0 in 14 tissues) exposures (p < 0.01). Mutations were not detected in RET, K-ras and beta-catenin genes. Expression analysis by GeneChip indicated that gene expression was also well maintained in the transplanted human thyroid tissues. However, lower doses (1 or 3 Gy) of 137Cs gamma-rays can induce changes in gene expression in the transplanted human thyroid tissues. Furthermore, fatally irradiated SCID mice could survive with human bone marrow cell transplantation. When about half of mouse bone marrows were replaced by human bone marrow cells, the human bone marrow cells showed high sensitivity to gamma-irradiation; 28.0% and 0.45% survival after 0.5 and 2.0 Gy exposures, respectively.     

Peculiarities of the ovary structure in the rat offspring developing under conditions of the removed thyroid gland of female rat with the thyroxine replacement therapy and external radiation exposure in utero

The influence of a single external gamma-radiation at a dose of 1.0 Gy (dose rate 9.08 x 10(-4) Gy/sec) on the 15th day of gestation in case of the removed complex of thyroid and parathyroid glands (thyroidparathyroidectomy) on the first day of gestation, as well as introduction of thyroxin and CaC12 on the structure of offspring ovary in postnatal ontogenesis (30-day old animals) was studied. It has been shown that thyroidparathyroidectomy of a female mother rat with thyroxine replacement therapy and irradiation, as well as the combination of these factors disturb the structure of ovarian tissues of the offspring. A single external irradiation on the 15th day of embryogenesis causes death of a considerable part of primordial follicles in the offspring ovary and growth of follicular layers in the secondary follicles. Thyroidparathyroidectomy of female rat on the first day of gestation with thyroxine replacement therapy causes delay in the development of follicles in the ovary at the early stages of maturation of 30-day old animals. The radiosensitivity of the ovarian tissues of the offspring that has been developed under the combined effect of the factors studied increases and results in an almost full loss of pool cells in the ovary of infant rats.     

Comparative results of thyroid ultrasound and laboratory studies in patients exposed to radiation

The paper presents the data of thyroid ultrasound and laboratory studies in 233 persons exposed to radiation: 63 X-ray physicians, 36 Chernobyl accident liquidators, 31 patients with lymphogranulomatosis, receiving radiotherapy, and 103 individuals (a control group) who were physicians of various specialties whose professional activity is unassociated with radiation factors. Thyroid changes were found in 67.7% of the examinees after gamma teletherapy and in 31% in the control group; among X-rat physicians and Chernobyl accident liquidators, the occurrence of thyroid changes was equal--44.4%. Direct radiation exposure of the thyroid in a dose of above 30 Gy led to the development of postradiation fibrosis (22.5%) and postradiation thyroiditis (32.3%) with thyroid dysfunction that is most commonly presented by hypothyroidism (22.45%). Autoimmune thyroiditis (11.1%) more predominantly with subclinical hypothyroidism, and diffuse thyroid hyperplasia (19.4%) resulted from mixed internal and external radiation. Thyroid changes revealed in X-ray physicians mainly appeared as nodular masses (22.2%) without functional impairments but to be followed up. It is recommended that the annual preventive examination protocol be supplemented by thyroid ultrasound studies in X-ray physicians.     

Is there a double pathway for the secretion of thyroglobulin: a "short circuit" weakly glycosyl-iodinated and a "long circuit" strongly glycosyl-iodinated?

Intact rat thyroid lobes incubated in vitro release recently synthesized thyroglobulin (Tg) into the media at a faster rate than they release thyroglobulin stored in follicular structures. Differential release of this Tg fraction cannot be explained by morphological alterations in thyroid architecture during incubation. This rapidly excreted fraction exhibits a low density on rubidium chloride gradients characteristic of poorly sialylated and poorly iodinated thyroglobulin, comigrating on rubidium chloride gradients with thyroglobulin isolated from tunicamycin treated glands. This poorly sialylated and poorly iodinated thyroglobulin is itself unaffected in its density or release into the media by tunicamycin treatment. Tg isolated from the media of tunicamycin treated glands has nearly the same low iodine and low sialic acid content as rat serum thyroglobulin and does not incorporate radiolabelled glucosamine. This fraction thus appear to duplicate properties of low glycosylated-low iodinated thyroglobulin released from thyroid cells in organisms that have no follicular structures and no follicular storage process as well as from thyroid tissue in patients with thyroid disease states, particularly thyroid tumors. Thus it is proposed a "short loop" pathway of low-glycosylated low-iodinated thyroglobulin directly into circulation, that bypasses and is not stored in the follicular lumen, the "long loop".     

Evaluation of p53 and soluble Fas ligand (sFasL) serum level concentration as indicators of apoptosis in serum of patients with benign and malignant primary follicular thyroid tumors

INTRODUCTION: Apoptosis (programmed cell death) is the best described mode of physiological cell death. During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is external protein signal originating from other cell--also named as "death signal". Another one is specific cell reaction for external stress factors. Blood concentration of proteins regulating both pathways of apoptosis may be useful in early diagnosis and staging of thyroid tumors. The aim of study was evaluation of p53 and sFasL blood concentration in patients with benign follicular adenoma and follicular thyroid cancer. MATERIALS AND METHODS: The study population was composed of 28 patients: 14 with thyroid carcinoma and 14 patients with follicular neoplasm (NF). All patients underwent surgical treatment. P53 and sFasL levels were evaluated before surgery and related to the histopathological diagnosis obtained post-surgery. RESULTS: The analysis revealed high sFasL blood concentration in patients with follicular thyroid cancer in comparison with the group with follicular adenoma. There was no statistically significant difference between levels of p53 in both groups. CONCLUSIONS: Evaluation of sFasL serum level concentration may be useful in preoperative diagnosis of follicular thyroid tumors.     

Morphofunctional characteristics of the thyroid gland in intact and partially sympathectomized rats of different age groups

The morphological and functional age-dependent changes have been studied in the thyroid gland of infantile (1-month-old), immature (2- and 3-month-old) and sexually mature (6-month-old) male rats. The decrease in thyroid functional activity with ageing was proved. Chemical sympathectomy (guanethidine at a dose of 15 mg/kg intramuscularly for 14 days after birth) was accompanied not only by morphological reconstruction of the thyroid tissue, but also (especially in 1-month-old rats) by a delay in transport-organic phase of iodine metabolism and a decline in thyroid hormone serum level. Later on, the compensatory hormonogenesis reinforcement occurs as a result of partial adrenergic innervation recovery.     

Cytogenetic effects in follicular epithelium of thyroid gland under prolonged exposure to gamma-radiation at low-doses

The forming processes of micronucleated follicular thyrocytes in thyroid gland of mature Wistar rats under exposure to the prolonged low-intensity gamma-radiation with 5 and 50 cGy (dose rates: 25, 400 microGy/h; duration: 55, 80 days) were investigated. The chronic exposure to low-intensity gamma-radiation in both doses invokes the frequency of micronuclated thyrocytes three times higher in comparison with control animals. As a result of the small-sized micronuclei formation prevalence in irradiated group, the average size of micronuclei was 1.4-2 times lower than control values. This phenomenon can be reproduced in model experiments with hemithyroidectomized animals exposured to acute gamma-radiation with 2-4 Gy. The obtained results show high sensitivity of micronucleus test to the early determination of radiation-induced genetic damages in follicular epithelium of thyroid gland.