Morphometric investigations on endocrine glands. V. Changes in the testes of Wistar rats after application of chlormadinone acetate and norethisterone acetate.

In growth inhibiting tests of rat testes the tubular diameter and, somewhat less sensitive, the nuclear volume of the Leydig cell follow the weight changes. Chlormadinone acetate shows antigonadotropic activity only at high doses and a dose-dependent antiandrogenic activity. The dose-weight curve under norethisterone acetate has a minimum at 4.2 mg/rat/14 days; higher doses seem to be accompanied by androgenic efficiency.     

Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1.

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.     

Production of thymocyte-stimulating activity by cultured human thyroid epithelial cells.

Since thyroid follicular epithelial cells (thyrocytes) have been shown to express a number of functions similar to monocytes, they were further examined for their potency in secreting thymocyte-stimulating activity (TSA). Although spontaneous production of TSA could not be detected when thyrocytes were cultured in the culture medium, TSA was demonstrated in the culture supernatants after stimulation with the immune adjuvant lentinan. The release of TSA was found in the culture supernatants collected 24 h after stimulation and was maintained for the 4 days of culture. Maximum levels of TSA release were achieved by 2 days. In addition, when culture supernatants of thyrocytes stimulated with lentinan or monocyte-derived interleukin 1 (IL-1) were incubated with a rabbit antibody to human IL-1, a parallel reduction in TSA was observed, suggesting that the active product in the thyrocyte culture supernatant shared a common antigenic site with IL-1. The demonstration of the production of IL-1 like activity by thyrocytes provides additional evidence that these cells, in addition to their functions as endocrine cells, may also participate in the local immune responses under appropriate conditions.     

Ultrastructure of the degradation of erythrocytes by thyroid epithelial cells in vivo.

The ultrastructure of the degradation of red blood cells (RBCs) in vivo by rat thyroid epithelial cells was studied. Two morphologically distinct degradative pathways appeared evident. The granular pathway was characterized by a finely mottled appearance of RBC phagosomes, first observed about the RBC periphery and later extending to the entire RBC matrix. Such phagosomes became gradually smaller, less electron dense, and indistinguishable from cellular lysosomes. The hemolytic degrative pathway was characterized by a progessive, usually homogenous decrease in the density of the RBC matrix except at the periphery of the RBC, where a thin, dense layer persisted for some time. Such phagosomes often appeared swollen relative to freshly ingested RBCs and resembled RBC ghosts. In later stages, they became irregular, smaller, and gradually indistinguishable from cellular lysosomes. Both degradative pathways were associated with ferritin-like particles. The earliest visualization of ferritin was in the cytoplasm, but in later stages it was also found to be concentrated within lysosomes and phagolysosomes.     

Secretory activity of goat mammary glands during pregnancy and the onset of lactation.

1. The volume of the udder and the composition of the secretion have been followed in five goats through pregnancy to the onset of lactation. 2. During the middle of pregnancy udder volume was minimal and there was little or no fluid in the teats. 3. Two stages of commencing secretory activity (lactogenesis) were defined. In the first, starting up to ten weeks pre-partum, udder volume increased and the fluid in the teats changed from an extracellular-fluid-like to a milk-like composition and acquired a high concentration of immunoglobulins. Four goats accumulated several litres of a pre-colostral fluid with a high [lactose] 6-7 weeks pre-partum. 4. Comparison of the rate of increase in udder volume with previous data for the rate of increase in empty udder volume in pregnant goats showed that the rate of secretion, even in the last few days of pregnancy, was only a few per cent of the rate immediately after parturition. 5. In the last 2-3 days of pregnancy there was a three to elevenfold increase in [citrate] in the secretion; this heralded the onset of copious secretion at about the time of parturition. 6. The changes in mammary gland activities are discussed in relation to changes in plasma hormone concentrations during pregnancy.     

Maintenance by androgen and thyroid hormone of androgen-induced convoluted tubular cells in mouse submandibular glands.

Injection of 5 alpha-dihydrotestosterone (DHT) into castrated adult female mice stimulated the proliferation of a small proportion of the convoluted tubular cells in the submandibular glands. We investigated the effects of DHT and thyroxine (T4) on the maintenance of these proliferated convoluted tubular cells. For this, castrated adult female mice that had been treated daily with DHT for 3 days and then once with [3H]thymidine, received a first series of daily injections of DHT for various periods or T4 for 10 days, and then a second series of injections of treatment with DHT or T4, or no further treatment. The second series of treatments with DHT or T4 maintained the percentages of 3H-labeled convoluted tubular cells at similar or slightly lower levels than those at the end of the first series of treatments. In mice that did not receive the second series of treatments, the percentages of 3H-labeled convoluted tubular cells decreased markedly, becoming significantly lower than those at the end of the second series of treatment with DHT or T4. We also examined the effect of DHT on the proliferation of convoluted tubular cells of castrated adult female mice that had received 10 daily injections of DHT and then no treatment for 28 days. In these mice, the cells did not proliferate markedly on stimulation with DHT. These results suggest that androgen and thyroid hormone maintain convoluted tubular cells that have proliferated in response to androgen, and that the convoluted tubular cells may become unresponsive to androgen in terms of proliferation after their exposure to androgen.     

Cytokine regulation of HLA on thyroid epithelial cells

The regulation of class I and class II HLA expression in human thyroid follicular cells was studied in vitro. Tumour necrosis factor-alpha (TNF-alpha) enhanced the expression of class I antigen on thyrocytes, but these cytokines had little effect on the expression of class II antigen. Interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) did not affect class I and class II antigen expression. The combination of interferon-gamma (IFN-gamma) with TNF-alpha or IL-1 beta enhanced the induction of class I and class II antigens, compared with the effect of IFN-gamma alone. Neither class I nor class II expression was induced by IL-6 alone or in combination with IFN-gamma. These findings suggest that TNF-alpha and IL-1 beta may have an important role in inappropriate expression of HLA antigens on thyrocytes in thyroid gland.     

Detection of in vivo production of tumour necrosis factor-alpha by human thyroid epithelial cells.

We have established previously that human thyroid epithelial cells (TEC) from patients with autoimmune thyroiditis are able to synthesize cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6). This paper examines TEC in sections from autoimmune thyroiditis for the in vivo production of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) using the combined techniques of in situ hybridization and immunohistochemistry. Thyroid tissue from patients with Graves' disease, Hashimoto's disease and non-toxic goitre was examined and both mRNA and the protein of TNF-alpha were detected in TEC on frozen sections. Representative figures of only Graves' samples are illustrated in this paper. In contrast, using the same methods, IFN-gamma was detected only in the infiltrating cells and not in TEC of thyroid tissue from the patients.     

The ultrastructural features of secretory cells of some endocrine glands in aging

In the electron microscopic investigation of the secretory cells of adenohypophysis, adrenal cortex, adrenal medulla and pancreatic islets from the adult and old Wistar male rats, certain age-related ultrastructural features have been found. Age changes appeared to be more pronounced in the thyrotrophs, somatotrophs and gonadotrophs of the adenohypophysis and in zona glomerulosa and zona reticularis spongiocytes of the adrenal cortex. They consisted of atrophy of the Golgi apparatus, appearance of the cytoplasmic vacuoles, lipid and lipofuscin granules, secondary lysosomes and damage of the inner mitochondrial membrane. Parallel to these, hypertrophy of the Golgi apparatus and rough endoplasmic reticulum, formation of giant mitochondria and presence of a great number of secretory cells in the cellular cytoplasm were noted in zona fasciculata spongiocytes and chromaffin cells of the adrenal medulla, and in beta cells of the pancreatic islets during aging thus evidencing for the adaptive changes in the ultrastructure of these cells. However, no appreciable age changes have been observed in the ultrastructure of the adrenocorticotropic cells of the adenohypophysis.     

Studies on an acquired inhibition of factor VIII induced by penicillin allergy.

An inhibitor of antihaemophilic globulin has been found in association with penicillin allergy. Inhibitor activity was detected after a severe reaction of penicillin. Neutralization studies showed the activity resided in an IgG globulin with kappa light chains. Experiments with insolubilized gammaglobulin demonstrated that the activity of the inhibitor was found in a specific penicillin antibody.     

In-vitro cultivation of human cytomegalovirus in thyroid epithelial cells

Summary Several strains of human cytomegalovirus including recent isolates, were grown in epithelial cells derived from thyroid tissue. All the strains tested grew in these cultures without pre-treatment of the cells, and no difference in cytopathic effect was detected between strains of genital and non-genital origin. 4 strains of CMV were isolated directly from urine in thyroid cells; however the failure to isolate 6 further strains in these cultures from other specimens may indicate that a higher multiplicity of infection is required to infect epithelial than fibroblast cells.With 1 Figure     

Expression of adhesion molecules on infiltrating T cells in thyroid glands from patients with Graves' disease.

The present study was performed to elucidate the role of adhesion molecules in the pathogenesis of Graves' disease. Peripheral blood and intrathyroidal mononuclear cells were obtained from 14 patients with Graves' disease. The expression of adhesion molecules and HLA-DR antigen on CD4+ cells and CD4+ cell subpopulations was analysed by the two- or three-colour immunofluorescence method. The expression of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells in the thyroid gland was markedly higher than that in peripheral blood. In peripheral blood CD4+ cell subsets, the CD4+ CD45RO+ cell population had an enhanced expression of the adhesion molecules compared with the CD4+ CD45RA+ cell population. However, there was no significant difference in the expression of adhesion molecules by CD4+ cell populations and subsets between Graves' disease and healthy subjects. The thyroid gland from Graves' disease contained a higher percentage of CD4+ CD45RO+ cells and a lower percentage of CD4+ CD45RA+ cells. In intrathyroidal CD4+ cell subsets, the CD4+ CD45RO+ cell population had an increased expression of LFA-1 and CD2 compared with the CD4+ CD45RA+ cell population, but there was no significant difference in VLA-4 and VLA-5 expression between the two cell subsets. Furthermore, the expression of LFA-1 and CD2 on the CD4+ CD45RO+ cell population in the thyroid was significantly higher than that in matched peripheral blood. A similar finding was also observed for the CD4+ CD45RA+ cell population. The thyroid gland had an increased percentage of CD4+ HLA-DR+ cells compared with matched or healthy peripheral blood. However, there was no significant difference in the percentage of HLA-DR+ cells in the thyroid gland between CD4+ CD45RO+ cell and CD4+ CD45RA+ cell populations. These results suggest that increased expression of adhesion molecules on CD4+ cells may be responsible for the migration of these cells into thyroid glands and cellular interactions between these cells and thyroid epithelial cells.     

Secretory activity of endocrine glands in gastroduodenal ulcer during late postoperative period]

The hormonal status of the endocrine glands (the hypophysis, thyroid, adrenals, pancreas, gastrin-producing cells of the stomach, gonads), was evaluated in patients with gastroduodenal ulcer operated (gastric resection, vagotomy) 6, 12 or 36 months before. Hormonal balance was found affected, the gonads underwent gross changes responsible for gonadal depletion in the long-term postoperative period. Recommendations for relevant correction are provided.     

Shape of large bound polysomes in cultured fibroblasts and thyroid epithelial cells.

Large bound polysomes were observed by conventional electron microscopy in surface or en face views of the rough endoplasmic reticulum (RER) in two cultured cell types. Cultured thyroid follicular epithelial cells and dermal fibroblasts, both from rats, were prepared for electron microscopy. Ultrathin sections were cut in the plane of the flattened cells to maximize the incidence of RER surface views. Some observations were also made on tissue sections of rat thyroid. Most of the large, RER-bound polysomes in both cell types appeared as two parallel rows of ribosome, thus resembling the shape of long hairpins, although probably closed at both ends. The two parallel rows of ribosomes were about 14 nm apart, and the center-to-center distance between ribosomes in the strands averaged 25 nm. Most of the large bound polysomes in thyroid epithelial cells were presumably making thyroglobulin subunits (330 kDa), while a majority of those in the fibroblasts were probably making prepro-alpha chains of collagen I (150 kDa). It was not possible in this material to see complete large polysomes, because their size usually caused them to extend out of the plane of section. In addition to the hairpin polysomes, there were smaller numbers of other forms. A characteristic large spiral polysome was seen occasionally in both cell types and contained as many as 31 ribosomes. One or two dense particles were sometimes seen in the center of spiral or circular polysomes. The consistent hairpin shape of most large bound polysomes observed in this study suggests that their shape is quite stable.