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H J Peter

Publications and source records attributed to H J Peter.

At least 19 recordsLinked to original sources

Differential expression of IgG Fc binding protein (FcgammaBP) in human normal thyroid tissue, thyroid adenomas and thyroid carcinomas.

The genetic events involved in thyroid carcinogenesis are still incompletely understood. Several rearrangements and mutations of oncogenes have been implicated in the development of thyroid papillary carcinomas, follicular adenomas and carcinomas. However, none of these molecular alterations is suitable either as a general marker for the diagnosis of thyroid carcinomas or to differentiate between thyroid follicular adenomas and carcinomas. In order to identify new genes with altered expression which could serve as such markers, we analyzed RNA from thyroid tumor and normal tissue using a novel technique called restriction-mediated differential display. Several differentially expressed genes were identified, including the gene for IgG Fc binding protein (FcgammaBP). Differential expression of FcgammaBP was confirmed by quantitative real-time RT-PCR. Our experiments showed that IgG Fc binding protein (FcgammaBP) is differentially expressed in normal thyroid tissue, thyroid adenomas and thyroid carcinomas. While the FcgammaBP gene is constitutively expressed in normal thyroid tissue, its expression is significantly increased in follicular thyroid adenomas and significantly decreased in papillary and follicular thyroid carcinomas. Thus, measurement of the expression levels of FcgammaBP in thyroid biopsies might help to make the otherwise difficult distinction between a thyroid follicular adenoma and a follicular carcinoma.

Adenoma↗

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues.

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

Adenoma↗

Growth hormone regulates growth hormone receptor gene transcription in primary human thyroid cells.

In this study the regulation of GH-receptor gene (GHR/GHBP) transcription by different concentrations of GH (0, 12.5, 25, 50, 150, 500 ng/ml) with and without variable TSH concentrations (0.5, 2, 20 mU/l) in primary human thyroid cells cultured in serum-free hormonally-defined medium was studied. The incubation time was 6 h and GHR/GHBP mRNA expression was quantitatively assessed by using PCR amplification at hourly intervals. Correlating with the GH-concentrations added a constant and significant increase of GHR/GHBP gene transcription was found. After the addition of 12.5 ng/ml GH, GHR/GHBP mRNA concentration remained constant over the incubation period of 6 h but in comparison with the experiments where no GH was added there was a significant change of GHR/GHBP mRNA expression. Following the addition of 25 ng/ml GH a slight but further increase of GHR/GHBP transcription products was seen which increased even more in the experiments where higher GH concentrations were used. These data focusing on GHR/GHBP gene transcription derived from cDNA synthesis and quantitative PCR amplification were confirmed by run-on experiments. Furthermore, cycloheximide did not affect these changes supporting the notion that GH stimulates GHR/GHBP gene transcription directly. In a second set of experiments, in combination with variable TSH levels, identical GH concentrations were used and no difference in either GHR/GHBP mRNA levels or in transcription rate (run-on experiments) could be found. In conclusion, we report data showing that primary thyroid cells express functional GH-receptors in which GH has a direct and dose dependent effect on the GHR/GHBP gene transcription. Furthermore, TSH does not a have a major impact on GHR/GHBP gene regulation.

Base Sequence↗

Colloidal aggregates of insoluble inclusions in human goiters.

To shed some light on the physicochemical properties of the thyroid follicular colloid, we have screened retrospectively the autoradiographs of 60 human nodular goiters labeled 17 h preoperatively with 100 microCi 125I for evidence of colloid compartmentalization. In 87% (52/60) of all goiters examined, sporadic or multiple colloidal inclusions ('colloid stones') not mixing with newly labeled Tg were detected. The detailed analysis of 17 goiters revealed a mean incidence of 0.09+/-0.11 'colloid stones' of variable size per follicle ranging from 0.02+/-0.01 (10) to 0.43+/-0.09 (5) (mean values +/- S.D., number of sections examined in brackets). In this study we did not find a clear-cut association of incidence of 'colloid stones' with sex, age or nosologic group (hyperthyroid, preclinically hyperthyroid, euthyroid). The existence of different colloidal compartments as demonstrated in this and other studies is of considerable importance for thyroid function, interpretation of iodine kinetics, and studies on the role of iodine on growth and function of the thyrocytes. Different thyroidal iodine compartments could well be of functional relevance, for example in the adaptation of thyroid hormone secretion to antithyroid drugs or in severe and prolonged iodine deficiency, when very slow compartments become an important source of minimal quantities of iodine and thyroid hormone. 'Colloid stones', for example, may well explain the repeatedly observed, surprisingly large total iodine store in human endemic goiters, even in the presence of severe iodine deficiency. It is evident that the existence of multiple iodine compartments and, in particular, of particulate slow-turnover pools complicates the interpretation of total glandular iodine measurements with modern techniques such as X-ray fluorescence and positron emission tomography.

Adult↗

Inhibition of iodine organification and regulation of follicular size in rat thyroid tissue in vitro.

The factors mediating the accumulation of thyroglobulin are of great importance to the understanding of the pathogenesis of human and experimentally induced colloid goiters. To elucidate further the underlying cellular mechanism, thyroid fragments from newborn rats were incorporated into semisolid alginate beads and were cultured as three-dimensional organoids for up to 21 d. In five parallel cultures, the medium contained either no supplements (group A), Nal (group B), thyroid-stimulating hormone (TSH) (group C), Nal plus TSH in the same concentrations as B and C (group D), or Nal and TSH (as in group D) plus methimazole (MMI, group E). The thyroid organoids maintained morphological integrity, functional activity, and ability to proliferate in vitro. Addition of iodine to the cultures significantly increased mean (+/-SEM) follicular diameters from 19.5 +/- 0.7 microm in controls to 33.9 +/- 2.2 microm (p < 0.0001) when NaI was added alone (group B), and 30.4 +/- 1.7 microm (p < 0.0001) when combined with TSH (group D). The effect of NaI on follicular size was abolished by MMI (group E, follicular diameter 23.5 +/- 1.3 microm). The results presented support the recent finding, using a rat colloid goiter model, that not only TSH but also iodine organification or its inhibition are important factors in modulating follicular morphology.

Animals↗

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis.

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.

Alginates↗

Morphological, immunohistochemical and autoradiographic studies of thyroid autonomy.

The values and limits of morphological, immunohistochemical and autoradiographic methods in studies of thyroid autonomy are briefly discussed. For meaningful studies of molecular aspects of thyroid autonomy--such as for example TSH receptor and Gs-alpha gene mutations--it is absolutely crucial that the tissue analysed is well characterized and really is autonomous. This is particularly important in view of the well known heterogeneity of human goiter tissue in respect to many if not all functional and proliferative parameters. To prove functional and proliferative autonomy of thyroid tissue, autoradiography is a very helpful tool, while simple morphology and immunohistochemistry do not contribute substantially to this aim.

Animals↗

Alginate gel culture allows the retention of extracellular matrix and follicular structure of rat thyroid tissue but does not lead to the formation of follicles by FRTL-5 cells.

Extracellular matrix (ECM) and basement membrane (BM) components were studied by immunohistological methods in native rat thyroid tissue, and in rat thyroid tissue and FRTL-5 cells cultured in a three-dimensional alginate bead system. In all three situations, the presence of collagen IV, laminin, perlecan, and fibronectin was demonstrated. There were marked differences between rat thyroid tissue and FRTL-5 cells in culture. Rat thyroid tissue maintained a follicular structure, whereas FRTL-5 cells did not form follicles. Rat thyroid cells multiplied more slowly than FRTL-5 cells and thyroglobulin (Tg) was visible in the follicular lumen, while in FRTL-5 cells Tg was only seen intracellularly. Tg iodination was much lower in FRTL-5 cells than in rat cells. In rat thyroid cells, positive staining for collagen IV, laminin, and perlecan was seen in thin membranes around individual follicles, and for fibronectin around groups of follicles. In FRTL-5 cells, these ECM/BM components could be identified, but were not organized into equally regular networks around groups of cells. These results demonstrate that of the two types of cells examined, primary cultures of rat thyroid cells in alginate beads maintain structural and functional similarities to native thyroid tissue and would therefore be suitable for future in vitro studies of thyroidal ECM/BM and their interrelationship with growth and function of this organ. FRTL-5 cells cultured in alginate beads show some functional, but not structural similarities to native thyroid tissue and so would be less valuable for use in such studies.

Alginates↗

Expression patterns of extracellular matrix components in native and cultured normal human thyroid tissue and in human toxic adenoma tissue.

The extracellular matrix (ECM) and basement membranes (BM, a specialized form of ECM) greatly influence proliferation, differentiation, and function of cells and the structure of tissues. While a considerable amount of information is available on thyroid cellular proliferation, differentiation and function, much less is known about thyroid ECM and BM. In this study the presence of the ECM/BM components fibronectin, collagen IV, alpha1, beta1, gamma1 laminin, several laminin variants, osteonectin, and perlecan was demonstrated in cryosections of nonadenomatous and toxic adenoma human thyroid tissue. Also, positive immunohistochemical staining for collagen IV, laminin, perlecan, and fibronectin was obtained in sections of human thyroid tissue cultured in a three-dimensional (alginate) culture system. The present study provides methods and data that will facilitate the investigation of the interaction between cells and ECM in thyroid tissue.

Adenoma↗

Model of the athymic nude mouse for the study of benign goiter disease.

Since Shimosato et al., in the mid 70s transplanted for the first time thyroid carcinoma tissue onto nude mice, other research groups have made use of the nude mouse model for the investigation of xenotransplanted thyroid tissue. The use of this model for the investigation of benign goiters is briefly discussed in this article. Normal human thyroid tissue has been transplanted either as a control in experiments with benign and malignant goiter tissue, or for the study of thyroid tissue response to stimulators such as TSH or thyroid stimulating antibodies (TSAb). Thyroid glands from 8- to 10-week old human fetuses obtained at the time of legal abortion were cryopreserved in liquid nitrogen and successfully transplanted into nude mice. Moreover, all the variants of human benign goiter tissue have been xenotransplanted: tissue from nodular and diffuse goiters, hot and cold nodules or goiter areas, rapidly growing nodules, etc. Two examples of animal thyroid tissue xenotransplantation onto nude mice are briefly discussed: Nude mice bearing normal thyroid tissue transplants from 4 different species (man, rat, pig, guinea-pig) have been used for the study of the species specific effect of bovine TSH and TSAb. In studies aiming at elucidating the pathogenesis of hyperthyroidism, toxic goiter tissue from hyperthyroid cats has been transplanted. In methodological terms, these experiments have shown that surgically removed goiter tissue can be shipped by air in cell culture medium at 4 degrees C over long distances and then successfully transplanted.-Finally, cell lines such as the rat cell line FRTL-5 can be transplanted onto nude mice either as cell suspension or embedded in collagen, for example for the study of proliferation and folliculogenesis. Using the xenotransplantation model, function and proliferation, morphogenesis and differentiation, as well as thyroid autonomy and response to stimulators have all been studied in xenotransplanted human and animal thyroid thyroid tissue and cell lines under various experimental conditions. Although new research tools, for example transgenic animals, are now increasingly and successfully used, xenotransplantation still offers the possibility of addressing some specific questions which cannot be answered so easily with other experimental models. For example, studies with human tissue, involving drugs or radioactive tracers which cannot be applied to the intact human being, can relatively easily be performed with xenotransplanted human tissue and application of the drug or tracer to the host mouse. Or embryological development can be followed and studied using fetal thyroid (and other) tissue transplanted onto nude mice; here, of course, difficult ethical issues have to be considered. Finally, it should be mentioned that, although many scientific questions can be studied nowadays by cell culture or other in vitro systems, animal models are still needed. Extrapolation to the human being, however, should always be done with caution and we should always keep in mind that for the understanding of a human disease indeed human experimental models remain the goldstandard.

Animals↗

[Clinical aspects, diagnosis and drug therapy of hyperthyroidism].

Graves' disease and toxic uni- or multinodular goiter are the most frequent causes of hyperthyroidism. Graves' disease is caused by thyroid stimulating immunoglobulins which are directed against the TSH receptor of thyroid follicular cells. Graves' disease affects more females than males and is associated with diffuse goiter and a rapid appearance of symptoms and signs of hyperthyroidism. Patients with Graves' disease are on average younger than patients with toxic nodular goiter. The diagnosis of Graves' disease is usually easy, particularly if signs of endocrine opthalmopathy are present. Toxic nodular goiter is seen more often in older patients with pre-existing goiters. Symptoms and signs of hyperthyroidism often appear only slowly. Hyperthyroidism in these older patients can be oligosymptomatic. Older patients should therefore be investigated for the presence of hyperthyroidism, even if they present only a few symptoms or signs which could suggest this diagnosis. The development of ultrasensitive TSH assays has simplified the diagnosis of hyperthyroidism and made the TRH-test, often used in the past, almost superfluous. At the present time, it is practically always possible to differentiate between Graves' disease and toxic nodular goiter as the cause of hyperthyroidism on the basis of clinical and laboratory findings alone, and in many cases thyroid scintiscans are therefore no longer necessary. A patient with newly diagnosed Graves' disease is treated with antithyroid drugs (carbimazole or PTU) for one year. If hyperthyroidism persists after this one year of antithyroid drug treatment, or if it recurs, another year of therapy with carbimazole or PTU is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin.

Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland.

Animals↗

Effect of human thyroid stimulating autoantibodies on the radioiodine uptake of the mouse thyroid gland.

Administration of sera from patients with active Graves' disease to nude mice bearing human thyroid xenografts provides the opportunity to compare directly the effects of TSAb on thyroid tissue of different species. The results presented in this paper, namely the fact that only one of 8 Graves' sera increased the RAIU of the nu/nu mouse thyroids modestly while all sera increased the RAIU in the transplanted human tissue considerable, clearly show a species specific effect of TSAb.

Animals↗

Clonal analysis of human tumors with M27 beta, a highly informative polymorphic X chromosomal probe.

The clonality of human tumors can be studied by X inactivation/methylation analysis in female patients heterozygous for X-linked DNA polymorphisms. We present a detailed study on clonal tumor analysis with M27 beta, a highly informative probe detecting a polymorphic X chromosomal locus, DXS255. The polymorphism detected at this locus is due to variable numbers of tandem repeats. The rate of constitutional heterozygosity detected by M27 beta was 88%. Normal tissue from gastrointestinal mucosa and thyroid showed random, hence polyclonal, patterns. Nonrandom clonal X inactivation was detected in all 22 malignant neoplasms that had been shown to be clonal by other DNA markers, such as antigen receptor gene rearrangements or clonal loss of heterozygosity at 17p and other loci. 16/48 normal blood leukocyte samples (33%) showed considerably skewed X inactivation patterns. Comparison of blood leukocytes and normal tissue indicated that in a given individual, X inactivation patterns may be tissue specific. M27 beta was used to study the clonal composition of 13 benign thyroid nodules from 12 multinodular goiters with rapid recent growth, traditionally termed "adenomas." Nine of them were clonal, whereas four nodules and tissue from a case of Graves' goiter were not, indicating that some, but not all, such thyroid nodules may represent true clonal neoplasms. The M27 beta probe permits one to study the clonal composition by the X inactivation approach of a wide variety of solid tumors from most female patients. As a control, normal tissue homologous to the tumor type of interest is preferable to DNA from blood leukocytes, since the latter may show nonrandom X inactivation patterns in a fairly high proportion of cases. M27 beta may, therefore, be of limited use for the clonal analysis of neoplasms derived from hematopoietic cells.

Clone Cells↗

Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells.

This study was aimed at dissecting the cellular mechanisms that underly the growth of actively expanding human goiter nodules. Thirty-two nodules from different patients, all removed because of steady recent growth, were serially sectioned and screened for 1) histomorphological signs of cell proliferation and 2) in situ expression of the immunohistochemically stained p21ras protooncogene product. Bovine, porcine, and rat thyroid glands (the latter from both T4- and perchlorate-treated animals) were used as controls. In normal glands, only a few follicular cells contain substantial amounts of stainable p21ras. Some of these cells are unusually large, but do not proliferate. In contrast, all goiter nodules contain areas where the epithelial cells are morphologically grossly altered and heavily loaded with p21ras. Cells of this type are mostly clustered in large cohorts coating whole follicles or entire groups of follicles. Only a small fraction of these activated cells actually proliferates at any one point in time. Actively replicating cells are scattered in tiny foci all over the nodules. The earliest proliferating buds are solid, but soon begin to generate microfollicles that enlarge by adding new cells to the follicular epithelium. Regionally heterogeneous p21ras content in morphologically identical cells suggests that growth occurs in bursts and waves. We conclude that goiter nodules grow by episodic proliferation of heterogeneous cohorts of epithelial cells from which new follicles are generated. Only a tiny fraction of all goiter cells proliferate at any one point in time. The molecular mechanisms governing these growth processes are unknown.

Adolescent↗

Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism.

Spontaneous feline hyperthyroidism is a unique experimental model of toxic nodular goiter. To determine whether feline toxic goiter is caused by extrathyroidal stimulating factors or by the intrinsic autonomy of follicular cells, primary cultures of enzymatically dissociated follicles from 15 hyperthyroid cat goiters and from 3 normal cat thyroid glands were embedded in collagen gels. Growth and function in chemically defined media were assessed by autoradiography after double labeling with 3H-thymidine and 131I-Na. Iodine organification in follicles from normal glands was TSH dependent, but intense radioiodine organification occurred in follicles from hyperfunctioning goiters even in the absence of TSH. Similarly, twice as many follicular cells of hyperfunctioning thyroid tissue, maintained without TSH in the medium, were labeled after exposure to 3H-thymidine than in follicles from normal glands. The results strongly suggest that intrinsic alterations of cell function lead to autonomy of follicular growth and function and subsequently to the development of hyperplastic nodules, causing thyrotoxicosis. The reason for the focal nature of the disease remains an unresolved challenge. Further investigation using this model may further understanding of the growth of autonomous endocrine tumors.

Animals↗

Comparison of FRTL-5 cell growth in vitro with that of xenotransplanted cells and the thyroid of the recipient mouse.

The present work was designed to compare in vitro cell growth kinetics with in vivo growth under conditions as similar as possible using labeling with [3H]thymidine. To this purpose, FRTL-5 cells were cultured as monolayers and as three-dimensional spheroids embedded in collagen gels and transplanted simultaneously into nude mice treated with perchlorate and a low iodine diet. The growth of the transplants was compared to that of the thyroids in host mice. In the intact thyroid, the fraction of [3H]thymidine-labeled follicular cells (FLC; 24-h labeling) increased sluggishly to a maximum of 10% after 3 weeks of goitrogen exposure, with a subsequent autoregulatory decrease to 3% at 7 weeks. A 4-fold higher FLC was found in six adenomas, indicating focal failure of growth-restraining mechanisms. In nonconfluent monolayer cultures the FLC was as high as 90%, even within large individual clusters where cells are in tight mutual contact. Solid, highly cellular grafts growing from transplanted monodispersed cells showed an average FLC of 20%, which is 5 times higher than the FLC in the identically stimulated mouse thyroid. In collagen-embedded cells, forming three-dimensional spheroids, the mean FLC decreased from 70% at 1 week in vitro (40% in vivo) to 20% at 3 weeks both in vitro and in vivo, suggesting effective auto-regulation of excessive growth in both conditions. However, these FLC were again much higher than the 3% FLC in simultaneously assessed host thyroids. The difference remained throughout the 45-day period studied. We conclude that FRTL-5 cells growing as monolayers and as three-dimensional spheroids in vitro or after xenotransplantation in vivo invariably show much higher proliferation rates under comparable environmental conditions than the normal follicular epithelium in the thyroids of host mice. The one exception is the confluent monolayer with near-zero growth, while densely packed three-dimensional transplants still grow intensively. Although growth-retarding cell to cell interactions are also clearly operative in growing FRTL-5 cells, they are less effective than those dampening the replication rate of the thyrocytes within the monolayer hull of normal follicles. A local failure of these mechanisms, allowing growth rates comparable to those of grafted FRTL-5 cells results in adenoma formation in normal thyroids. These observations call for caution in the transfer of in vitro growth studies with FRTL-5 cells to in vivo conditions prevailing in the normal thyroid.

Adenoma↗

Thyroid cell lines in research on goitrogenesis.

Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.

Animals↗