Biomedical subjects

M C Many

Publications and source records attributed to M C Many.

At least 37 records · Page 2Linked to original sources

PubMed1995

The autoimmune response induced by immunising female mice with recombinant human thyrotropin receptor varies with the genetic background.

In a previous study, we have described the induction of thyroid blocking (TBAB) and thyrotropin binding inhibiting antibodies accompanied by thyroiditis in female BALBc mice (H2d) immunised with the extra-cellular domain (ECD) of the human thyrotropin receptor (TSHR) expressed as a maltose binding protein (MBP) fusion. In the present study we have investigated the response induced in mice of varying MHC haplotype. Two groups of female NOD (H2g), CBA (H2k) and C57 (H2b) mice were immunised intra-peritoneally with MBP-ECD or MBP on days 0 (100 micrograms), 15, 30 and 43 (50 micrograms). Blood samples from individual mice were obtained on days 0, 22, 36 and 50 and assessed for thyroid binding inhibiting immunoglobulins (TBII), thyroid stimulating (TSAB) and TBAB. On day 50 the treated mice and five age/sex matched NOD mice were sacrificed, their thyroids removed, examined histologically and any infiltrate characterised. Induction of antibodies to the ECD was tested by ELISA in which plates had been coated with either MBP-ECD or an ECD-protein A fusion. All of the mice developed a strong antibody response to the relevant immunogen but none of them contained TBII, TSAB or TBAB activities. No lymphocytic infiltration of the thyroid glands of the CBA or C57 mice was observed. In contrast, all of the NOD mice displayed severe thyroiditis, whilst one of seven MBP-treated mice had moderate infiltration and none of five untreated controls. Immunohistochemical analysis revealed that the infiltrate was predominantly activated T helper cells with little evidence of B cells or the cytokines IL-10 or IL-4, indicating that a Th1 response had been induced, contrary to our findings in BALBc mice which mount a Th2 response. In conclusion we have shown that the type and extent of response induced by immunising with the TSHR varies in mice of differing genetic background. H2d mice develop thyroiditis and TBAB/TBII, H2g mice develop thyroiditis in the absence of functional TSHR antibodies, whilst H2b and H2k mice are resistant.

Animals↗

PubMed1995

Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism.

It has been suggested that selenium deficiency is a co-factor to iodine deficiency in the pathogenesis of myxoedematous cretinism. The mechanism proposed is that the generation of hydrogen peroxide is greatly increased in iodine-deficient thyroid glands, and that selenium is involved in the control of hydrogen peroxide and its derived free radicals. This study was carried out to investigate the effect of the possibly impaired cellular defence mechanism associated with selenium deficiency on thyroid necrosis and tissue repair. For this purpose, we studied thyroid tissue from selenium- (SE-) and/or iodine-deficient (I-) rats before and after an acute toxic iodine overload. In I- thyroids, necrotic cells were numerous. Acute iodine administration increased this effect. Necrosis was associated with transient infiltration of inflammatory cells. In I-SE+ thyroids the tissue resumed its normal appearance. In I-SE- thyroid glands, the iodide toxicity was stronger, with greater necrosis and inflammatory reaction. The inflammation resolved but was replaced by fibrotic tissue. Fifteen days after the toxic overload, the connective tissue volume was twice the control value. Before iodide overload, the proportion of dividing cells was equal in I-SE+ and I-SE- thyroids. Three days after the iodide overload, this proportion was increased in I-SE+ thyroids but reduced in the I-SE- thyroids. Overall, the I-SE- thyroids had four times fewer dividing cells than the I-SE+ thyroids. In summary, selenium deficiency coupled to iodine deficiency increased necrosis, induced fibrosis and impeded compensatory epithelial cell proliferation. These results are compatible with histological and functional description of thyroid tissue from myxoedematous cretins.

Animals↗

PubMed1995

Two-step development of Hashimoto-like thyroiditis in genetically autoimmune prone non-obese diabetic mice: effects of iodine-induced cell necrosis.

The administration of a high iodide dose (HID; 10 micrograms/day) to goitrous mice is known to induce thyroid cell necrosis and inflammation, which, in most strains, is transient. In this study, we analyzed the effects of iodide in autoimmune prone non-obese diabetic (NOD) mice. Control NOD mice fed a standard diet (MID; 1 microgram I/day) or HID did not spontaneously develop thyroiditis. In NOD mice previously made goitrous, HID provoked thyroid cell necrosis and diffuse inflammation within 4 days. Inflammatory cells consisted of MHC-class II+ antigen-presenting cells, CD4+ T helper cells and CD8+ T suppressor/cytotoxic cells. After 96 days of treatment with HID, thyroiditis similar to Hashimoto's disease was obtained in 100% of the animals, with destruction of thyroid follicles, large clusters of T and B cells, and antithyroid antibodies in the plasma. When treating goitrous mice with MID, no cell necrosis was observed and no autoimmune thyroiditis was obtained. The early iodide-induced cell necrosis and inflammation may thus be considered as an important factor in the induction and persistence of autoimmune thyroiditis in individuals carrying a genetic susceptibility to autoimmune disease.

Animals↗

PubMed1994

Recombinant thyrotropin receptor and the induction of autoimmune thyroid disease in BALB/c mice: a new animal model.

In a preliminary study, we observed the production of TSH binding-inhibiting (TBII) and thyroid-blocking (TBAb) antibodies accompanied by lymphocytic infiltration of the thyroid in a pool of male BALB/c mice immunized with the extracellular domain (ECD) of the human TSH receptor (TSHR) expressed as a maltose-binding protein (MBP) fusion in bacteria. In the present study we evaluated the humoral response to the same antigenic preparation in a new series of individual male and female BALB/c mice immunized ip on day 0 with 100 micrograms MBP-ECD and days 25, 39, and 53 with 50 micrograms MBP-ECD in an adjuvant composed of aluminum oxide, magnesium hydroxide, and Bordetella pertussis vaccine. Mice immunized with MBP served as control. Individual sera and immunoglobulins were tested for TBII, TBAb, and thyroid-stimulating antibodies (TSAb) on days 0, 32, 46, and 60, and total circulating T4 levels were measured by RIA. Animals were killed on day 120, their thyroids were examined histologically, the infiltrates were characterized using monoclonal antibodies specific for T-cells (total, activated, helper, and suppressor), B-cells, and macrophages. Sera and immunoglobulins G of the MBP-treated control group were all negative for TSAb, TBAb, and TBII activity. The receptor-immunized mice, despite having high titers of antibodies to the immunogen in an enzyme-linked immunosorbent assay, displayed a heterogeneous response in terms of biological activity, with 3 of 7 female and 4 of 8 male mice having TBAb/TBII activities that persisted and whose activity increased throughout the experiment. No significant TSAb antibody activity was observed. Total T4 levels were also heterogeneous even before immunization, but 9 of 15 MBP-ECD-treated mice had levels below the normal range after immunization, and 7 of these also had TBII/TBAb activities. At the end of the experiment, only 4 of the MBP-ECD-treated female mice survived, but all of them had a severe lymphocytic infiltration of their thyroid, composed mostly of activated T-cells, although B-cells and macrophages were also present. A similar infiltrate was seen in 4 of 8 male MBP-ECD-treated mice. No infiltrate was observed in male or female MBP-treated mice. The model described demonstrates the feasibility of using the TSHR as an immunogen to overcome tolerance and mimics some characteristics of human autoimmune disease of the thyroid.

Animals↗

PubMed1994

Involvement of T cell immunity in the transient thyroid inflammation induced by iodide in goitrous BALB/C and nude mice.

To evaluate the involvement of T cell immunity in the thyroiditis induced in goitrous mice by iodide administration, we analyzed the immunological changes happening in the thyroid glands and lymph nodes during goiter involution in balb/c and athymic nude mice of similar background. In both balb/c and nude mice, goiter involution was characterized by thyroid cell necrosis and inflammation. In balb/c mice, the inflammatory infiltrate was made of numerous Ia+ cells. Their number was unchanged during goiter development, but was significantly increased after 2 days of involution and remained high after 8 days. CD4+ and CD8+ T cells were also observed, some of which were clearly activated since they expressed the receptor for Interleukin-2 (IL-2R). The numbers of CD4+, CD8+ and IL-2R+ T cells were increased during goiter as compared to control mice, and they reached a maximum at day 1 of involution. In nude mice, unexpectedly, CD4+ and CD8+ T cells were also found in the thyroid. Their numbers, as well as the number of Ia+ cells, were significantly increased at the onset of involution, but they remained systematically lower than in the corresponding groups of balb/c mice. Iodide treatment of goitrous mice also induced modifications of the lymph nodes draining the thyroid: enlargement of the paracortical T zone, presence of germinal centers in cortical follicles, and increase of the density of IL-2R+ cells. Mesenteric lymph nodes taken as controls were unchanged. Thus, three observations suggest the involvement of T cell immunity in iodine-induced thyroid inflammation: 1. Infiltration of Ia+, CD4+, CD8+ and IL-2R+ cells. 2. Signs of stimulation in thyroid lymph nodes, 3. Significant differences between balb/c and nude mice, in which the inflammatory reaction is weaker.

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PubMed1993

Selenium deficiency aggravates the necrotizing effects of a high iodide dose in iodine deficient rats.

The effect of selenium deficiency associated with various iodide intake was investigated in rats in order to better understand its possible role in the etiopathogeny of myxedematous cretinism. Groups of rat pups were fed from birth a low selenium diet (Se-) and submitted to goitrogenic treatment (1% perchlorate in water) for one month. Some animals were refed iodide after perchlorate withdrawal. The gland morphology was analyzed in correlation with the glutathione peroxidase (GPX) activity and the thyroid hormone plasma levels. In all Se- rats, the GPX activity was strongly reduced as compared to selenium sufficient (Se+) animals (P < 0.01). Goitrous rats were hypothyroid whatever the selenium intake. After iodide refeeding, plasma T4 and T3 levels were increased by 160% in Se- rats and by respectively 330% and 580% in Se+ rats. The thyroid morphology was different according to the selenium intake: necrotic cells were about three times more numerous in Se- than in Se+ rats (P < 0.01) and the inflammatory reaction was increased. These experimental data demonstrate the detrimental role of selenium deficiency in one experimental case of thyroid disease. Such reduction of cell defences could contribute to the thyroid failure of African myxedematous cretins.

Animals↗

PubMed1993

High frequency of thymic ectopy in thyroids from autoimmune prone nonobese diabetic female mice.

BACKGROUND: The female nonobese diabetic (NOD) mouse, a well known experimental model to study autoimmune type 1 diabetes, also spontaneously develops thyroiditis. In this study, we report an abnormally high frequency of thymic ectopy in thyroids from NOD mice. EXPERIMENTAL DESIGN: Thyroids and thymuses from NOD mice and from control mice of different strains were processed for light and electron microscopy and for immunohistochemistry. RESULTS: Ectopic thymic tissue was observed in the thyroids of 80% of female NOD mice, whereas it was not found in control age-paired female mice from various other strains. The thymic tissue was present beneath the capsule as a large and unique fragment consisting of both a cortical dark one and a medullary light region. Thymic ectopies, as the thymus itself, contained thymocytes expressing both L3T4 and Lyt2 antigens, specific respectively for T helper and T suppressor/cytotoxic cells. Cortical and medullary epithelial cells were also easily identified by electron microscopy and by immunohistochemical staining using ER-TR4 and ER-TR5 monoclonal antibodies. CONCLUSIONS: Our observation could be an indication for a relation between abnormal thymus development and autoimmune disorder such as thyroiditis.

Animals↗

PubMed1992

In vitro study of acute toxic effects of high iodide doses in human thyroid follicles.

The acute effects of increasing doses of sodium iodide were studied on human thyroid follicles isolated from normal paranodular tissue. After 24 h incubation in culture medium, follicles isolated from most thyroids maintained their capacity for 125I accumulation and organification and a normal cellular ultrastructure. 125I accumulation was significantly increased after addition of TSH, whereas 125I organification was not affected. In presence of TSH, numerous follicles had large empty-looking follicular lumina unlabeled on autoradiographies. Follicles incubated for 24 h in the presence of a low concentration (10(-7) M) of iodide retained their function and morphology. However, incubation with a high dose of iodide (10(-3) M) caused marked inhibition of 125I accumulation and organification reaching values similar to those obtained in presence of inhibitors of iodide trapping and organification. At high doses, iodide induced necrosis of thyroid epithelial cells: the percentage of necrotic cells was significantly increased with 10(-5) M and doubled with 10(-3) M as compared to values measured at 10(-7) M. Ultrastructural lesions such as apical blebbing, cytoplasmic fragments desquamation, endoplasmic reticulum vesiculation, and accumulation of lipofuscin in secondary lysosomes were also present. The necrotic effect and the ultrastructural alterations also occurred in the presence of TSH but were prevented by the addition of inhibitors of iodide trapping or organification. These results demonstrate a direct acute toxic effect of iodide in human thyroid cells. The nature of the ultrastructural alterations is in agreement with a mechanism of toxicity involving a free radical attack and lipid peroxidation as observed in other tissues.

Cytoplasm↗

PubMed1992

Iodine and goiter involution.

Iodine administration, although efficient in goiter treatment or prevention, is also responsible for adverse effects such as cell necrosis or thyroiditis. These two effects were reproduced in iodide-treated goitrous mice. Morphological observations strongly suggest that thyroid cell death results from an excessive production of free radicals, which initiates lipid peroxidation. This hypothesis is strengthened by the facts that the thyroidal concentration of malonic dialdehyde, a stable product of lipid peroxidation, is increased, and that necrosis is partially prevented by free radicals scavengers. Epithelial necrosis is associated to an inflammatory reaction. The infiltrate is mainly made of cells expressing class II molecules of major histocompatibility complex (macrophages and dendritic cells), but also of T lymphocytes. However, this inflammation, which varies among mouse strains, is transient and it is not amplified or maintained by administration of cytokines, IFN gamma or TNF alpha, known to induce class II expression on thyrocytes.

Animals↗

PubMed1990

Correlated autoradiographic and ion-microscopic study of the role of iodine in the formation of "cold" follicles in young and old mice.

The role of iodine in the formation of "cold" follicles (not labeled on autoradiograms after radioiodine administration) was analysed in ICR female mice during aging and involution of thyroid hyperplasia, by use of light and electron microscopy and by comparing autoradiographic and analytical ion-microscopic images for the same follicle in serial sections. The proportion of "cold" and "partly cold" (displaying a patchy or ring labeling pattern on autoradiograms) follicles increased significantly during aging. This increase was more pronounced in old mice fed an iodine-rich diet as compared to mice fed a moderate iodine diet. Similarly, during goiter involution produced by refeeding iodine, the follicular heterogeneity of iodine metabolism was more accentuated with a high dose of iodine, regardless of the age of the mice. The follicular lumina of "hot" and "cold" follicles had the same concentration of stable iodine, as shown by analytical ion microscopy, and the cells of both types of follicles formed colloid droplets in response to TSH. Furthermore, when a goitrogenic treatment was induced in aged mice, some "cold" follicles persisted after 8 days, but all follicles resumed "hot" after 16 days. By analytical ion microscopy, 127iodine was also found inside thyroid cells of old mice, but the cytoplasmic patches of 127iodine were not labeled with 125iodine. They corresponded to lipofuscin pigments and secondary lysosomes, as observed in serial sections at the electron-microscopic level. This intracellular stable iodine could constitute a slow turnover compartment not used for hormone synthesis.

Aging↗

PubMed1990

Effects of iodide on class II-MHC antigen expression in iodine deficient hyperplastic thyroid glands.

The expression of major histocompatibility complex class II molecules (Ia antigen) has been analyzed by immunoperoxidase staining in thyroids of normal C3H mice, of iodine-deficient mice with a hyperplastic goiter and of mice during goiter involution induced by administration of either a high iodide dose (HID, 10 micrograms/day) for 0.5 to 8 days or a moderate iodide dose (MID, 1 microgram/day) or triiodothyronine (T3, 1 micrograms/day) for 2 days. In normal and in hyperplastic thyroids, few interstitial cells were Ia positive (monoclonal antibodies, mAb, M5/114, ER-TR3). Their number was unchanged when goiter involution was induced by MID or by T3, but was significantly increased (p less than 0.05) after HID. It was maximal at days 1 and 2 of involution, decreased thereafter but remained higher (p less than 0.05) than in controls after 8 days. The Ia positive cells were mainly macrophages and, to a lesser extent, dendritic cells. Macrophages were identified by their heterogeneous content and their numerous lysosomes. They were stained with anti-Mac-1 (M1/70) and anti-Mac-2 (M3/38) mAb. Dendritic cells were characterized by their slender cytoplasmic processes, indented nucleus and pale cytoplasm. They were positive for NLDC-145 and MIDC-8 mAb whose specificity for dendritic cells has been demonstrated in lymphoid organs. During the whole period of involution analyzed, Ia antigens were not expressed on follicular cells. Since macrophages and dendritic cells are known to be involved in the pathogenesis of immune disorders, the inflammation induced by administration of HID to iodine-deficient mice could be considered as the early step of an immunological reaction.

Animals↗

PubMed1989

[Experimental goitrogenesis].

Various modern aspects of experimental goitrogenesis are reviewed and discussed. Regulation of follicular cell proliferation clearly involves several stimulatory but also inhibitory mechanisms. Furthermore, different stimuli are probably involved. Growth of the vascular and connective interstitial tissue probably involves paracrine factors and that of the follicles maybe autocrine factors; indeed, several growth factors are secreted by stimulated follicular cells. The formation of nodules is still poorly understood. They could derive from different cell populations or from cells being in different reactivity status with respect to the variations of the iodine fluxes in the gland. Finally, the relationship between iodine toxicity, nodularity and autoimmunity are discussed.

Aging↗

PubMed1986

Direct toxic effect of iodide in excess on iodine-deficient thyroid glands: epithelial necrosis and inflammation associated with lipofuscin accumulation.

Involution of thyroid hyperplasia (induced by a low iodine diet and a goitrogen, propylthiouracil, PTU) was obtained in mice by administering a high or a moderate dose of iodide (HID or MID, respectively). In HID involuting glands, vasoconstriction was observed after 12 hr whereas necrosis and inflammation were very abundant as early as after 6 hr and maximal after 48 hr. They were not prevented by papaverine by which vasoconstriction was inhibited, but were inhibited by the continuation of PTU by which iodide oxidation and organification were inhibited. Lipofuscin inclusions in thyroid and inflammatory cells were always associated with necrosis. On the contrary, when involution was induced by MID or by HID + triiodothyronine (T3), or by T3 alone, neither necrosis nor inflammation occurred and apoptosis was the only mode of cell deletion. No lipofuscin inclusion occurred. Our results demonstrate that iodide in excess, after being oxidized or organified, is directly toxic for iodine-deficient thyroid cells. The presence of lipofuscin suggests that its toxicity is mediated by lipid peroxidation, a consequence of production of free radicals in excess.

Animals↗

PubMed1986

Increased follicular heterogeneity in experimental colloid goiter produced by refeeding iodine excess after thyroid hyperplasia.

Delayed morphological changes induced in mouse hyperplastic thyroid by refeeding iodine were analyzed by light and electron microscopy, stereology, and autoradiography. Thyroid hyperplasia was induced by a low iodine diet supplemented with 0.25% propylthiouracil for 10 days. Involution was obtained by discontinuing the propylthiouracil and returning either to a moderate iodine diet [(MID) 1 microgram I/day] or to an iodine-rich diet [(HID) 10 micrograms I/day] for 40 days. In other experiments, three cycles of hyperplasia (8 days) and subsequent involution (8 days) with MID or HID were brought about. Control animals were fed MID or HID. All animals were killed when 12-14 weeks old after injection of 10-50 microCi 125I. Double labeling, with repeated injections of [3H]thymidine from day 0 to day 7 of involution followed by 125I injection 4 h before killing, was also performed. When involutions were performed with MID, most morphological variables returned to control values. However, when involution was brought about with HID, the glandular weight, the number of follicles, and the relative volume of follicular lumina remained larger than in controls. Moreover, the 125I-labeling pattern of the follicles was altered. The proportions of unlabeled, and unevenly or partly labeled, follicles, which were fewer than 5% in control groups, represented 25-35% of all follicles after involution with HID, whereas they were unchanged with MID. In unlabeled follicles the epithelium was flattened, with a reduced number of microvilli. Partly labeled follicles were of two types. In some follicles a persistent ring reaction was observed, suggesting an abnormally slow mixing of thyroglobulin. In others, the 125I labeling was restricted to areas adjacent to the apex of a reduced number of cells, suggesting that some cells were iodinating thyroglobulin, whereas others were not. There was no relationship between the follicular 125I labeling and the frequency of [3H]thymidine-labeled cells. These results indicate that refeeding iodine excess after hyperplasia leads to the formation of a colloid goiter with new follicles, and to an increased heterogeneity of iodine metabolism among follicles and among cells.

Animals↗

PubMed1986

Effects of iodide and thyroxine on iodine-deficient mouse thyroid: a morphological and functional study.

The effects of iodide and thyroxine (T4) on female mice fed a low iodine diet (LID) for 8 weeks were analysed by morphological, stereological and biochemical methods. Iodide was given at a dose of 10 micrograms/day (HID) or 1 microgram/day (MID), either alone or together with daily injections of 1 microgram T4 for 8 or 40 days. With HID, the thyroid weight and the numbers of follicles and cells remained higher than in controls, although cell necrosis occurred. Colloid volume increased and iodine was stored within the gland: a colloid goitre with non-functioning follicles was produced. With MID, the glands resumed an almost normal appearance. With T4 and LID, progressive normalization occurred, but after 40 days thyroid weight and numbers of follicles and cells remained higher than in controls. Glandular iodine content slowly increased and reached control value. The proportions of 125I-labelled tri-iodothyronine (T3) and T4 in thyroglobulin were reduced. With T4 and HID, the glands resumed a normal appearance. Neither necrosis nor folliculoneogenesis was noted. The proportions of 125I-labelled T3 and T4 in thyroglobulin were reduced, but T3 and T4 serum levels were higher than with HID. With T4 and MID, a normal state was obtained as early as day 8. After 40 days the gland was morphologically and functionally inactive. In conclusion, the association of T4 and iodide seems to be the best way to obtain a rapid and complete involution of thyroid hyperplasia. The administration of T4 prevents the deleterious effects of an excess of iodine on follicular cells, and causes the gland to enter a slow-functioning state.

Animals↗

PubMed1985

Morphological and functional changes during thyroid hyperplasia and involution in C3H mice: effects of iodine and 3,5,3'-triiodothyronine during involution.

Involution of thyroid hyperplasia was induced in mice by discontinuing a goitrogenic treatment (low iodine diet plus 0.25% propylthiouracil for 10 days) and returning either to a moderate iodine diet (MID; 1 microgram I/day) alone or associated with T3 administration (1 microgram/day) or to a high iodine diet (HID; 10 micrograms I/day) alone or associated with T3 treatment. Thyroid involution was studied by morphological, stereological, and biochemical methods after 2, 4, 6, and 8 days of involution. Age-paired, HID-fed animals were used as controls. When the involution was induced by MID, the glands resumed a normal morphological aspect. The synthesis and secretion of T3 were highly stimulated on day 2, but decreased thereafter. Plasma T4 levels reached a plateau at 50% of the control value from days 2-8. The administration of T3 together with MID accelerated the involution of hyperplasia and colloid accumulation in the follicular lumina. The synthesis and secretion of T3 and T4 remained lower than those in controls. When the involution was induced by HID, the thyroid weight remained higher than that in controls or in any involuting groups. The number of follicles and epithelial cells as well as the glandular thyroglobulin content were twice the control values. A Wolff-Chaikoff effect was evident on day 4, and hypothyroidism persisted. When HID was supplemented with T3 treatment, glandular weight and morphology were normal, but the Wolff-Chaikoff effect occurred earlier. In conclusion, the iodine dose given after a goitrogenic treatment must be carefully controlled; a high but physiological dose can have deleterious effects, whereas a small dose is beneficial. T3 prevents the deleterious effects of HID, but the thyroid enters a resting state.

Animals↗

PubMed1984

Precocity of the endothelial proliferation during a course of rapid goitrogenesis.

Thyroid hyperplasia was induced in C3H mice by a low iodine diet feeding supplemented with propylthiouracil. The morphological modifications associated to the development of hyperplasia were analyzed at light microscopical level and the cellular proliferation was studied by autoradiography after a pulse labelling with [3H]thymidine. The initial modification during the course of hyperplasia is the development of the vascularization. It includes the dilatation of the capillaries, which occurs before any extended modification of the follicular cells and any change of the thyroid weight, and the proliferation of endothelial cells which starts earlier than that of follicular cells.

Animals↗

PubMed1983

Morphological and functional changes during thyroid hyperplasia and involution in C3H Mice: evidence for folliculoneogenesis during involution.

Involution of thyroid hyperplasia was induced in C3H mice by discontinuing a goitrogenic treatment (low iodine diet supplemented with 0.25% propylthiouracil) and refeeding a normal iodine diet. Thyroid involution was studied by morphological, histochemical, autoradiographic, and stereological methods. The onset of the involution was characterized by an early accumulation of colloid, the presence of necrotic cells in the follicular lumina, and the appearance of homogeneous microcavities in the epithelial layers. The intraepithelial microcavities had the same morphological and functional properties as the follicular lumina. They were limited by a membrane covered with microvilli; polysaccharides and peroxidase activity were detected on their membranes, and 125I-labeling was marked in their lumina. Thin serial sections demonstrated that the microlumens originated from the intercellular space; plasma membranes differentiated into junctional complexes, and a narrow lumen limited by a membrane covered with short microvilli was formed in the intercellular space between the junctions. Later on, the newly formed microlumens fused to form new follicles with a cloverleaf pattern. As a consequence of the folliculogenesis, the total number of follicles doubled after 8 days of involution. This increase in number was mainly due to the presence of a population of small follicles. The folliculogenesis was associated in the first 4 days of involution with an active cellular multiplication which compensated for the early cell necrosis and led to a doubled number of epithelial cells. The increase in the total number of follicles and cells could partially explain the persistence of a relatively high thyroid weight after involution of hyperplasia.

Animals↗