Morphological and functional changes in several endocrine glands induced by hypothyroidism in the rat

The effect of hypothyroidism upon the morphology and the function of several endocrine glands was studied in radiothyroidectomized male rats. It was found that T3, T4, insulin, prolactin and corticosterone levels were significantly lower in hypothyroid rats. TSH levels were significantly higher in these animals while no changes were depicted in testosterone levels. The administration of T4 drew back to normal range the above-mentioned altered serum hormone levels. The studies performed with light microscopy revealed alterations only in the TSH secretory cells of the adenohypophysis. Conversely, when using the electron microscope to study the different endocrine glands, clear alterations were depicted in the TSH and prolactin secretory cells of the adenohypophysis, as well as in the pancreatic B cells and the cells of the zona fasciculata of the adrenal cortex. No abnormal changes were demonstrable at the level of the seminiferous tubules of the testis. All the above morphological changes were corrected by the administration of T4 to hypothyroid rats. These results suggest that the hypothyroid state is a complex hormonal dysfunction rather than a single hormonal defect. The secretory alterations are accompanied by fine cellular alterations in the corresponding glands.     

Tyrosine hydroxylase activity in the endocrine pancreas: changes induced by short-term dietary manipulation

BACKGROUND: Tyrosine hydroxylase (TH) activity and its possible participation in the control of insulin secretion were studied in pancreatic islets of adult Wistar rats fed a standard commercial diet (SD) or carbohydrates alone (CHD) for one week. TH activity, norepinephrine (NE) content, and glucose-induced insulin secretion were assessed. Blood glucose and insulin levels were measured at the time of sacrifice. RESULTS: CHD rats had significantly higher blood glucose and lower insulin levels than SD rats (114.5 PlusMinus; 6.7 vs 80.7 PlusMinus; 7.25 mg/dl, p < 0.001; 20.25 PlusMinus; 2.45 vs 42.5 PlusMinus; 4.99 &mgr;U/ml, p < 0.01, respectively). Whereas TH activity was significantly higher in CHD isolated islets (600 PlusMinus; 60 vs 330 PlusMinus; 40 pmol/mg protein/h; p < 0.001), NE content was significantly lower (18 PlusMinus; 1 vs 31 PlusMinus; 5 pmol/mg protein), suggesting that TH activity would be inhibited by the end-products of catecholamines (CAs) biosynthetic pathway. A similar TH activity was found in control and solarectomized rats (330 PlusMinus; 40 vs 300 PlusMinus; 80 pmol/mg protein/h), suggesting an endogenous rather than a neural origin of TH activity. CHD islets released significantly less insulin in response to glucose than SD islets (7.4 PlusMinus; 0.9 vs 11.4 PlusMinus; 1.1 ng/islet/h; p < 0.02). CONCLUSIONS: TH activity is present in islet cells; dietary manipulation simultaneously induces an increase in this activity together with a decrease in glucose-induced insulin secretion in rat islets. TH activity - and the consequent endogenous CAs turnover - would participate in the paracrine control of insulin secretion.     

Morphological changes in the endocrine pancreas of mice after treatment with streptozotocin combined with cyclophosphamide and neurotropin.

The effect of neurotropin (NSP) in combination with streptozotocin (STZ) and cyclophosphamide (CY) on blood glucose and pancreatic histopathology on day 7 and day 14 after the initiation of the treatment was studied in C57Bl/6 male mice. STZ (40 mg/kg) and NSP (1 mg/kg) were applied intraperitoneally on five consecutive days and CY (150 mg/kg)--twice on day 1 and day 3. In single B cells dilatation of the endoplasmic reticulum was found. On day 7 in proximity to some endocrine cells in the mice treated with STZ, STZ + CY + NSP and STZ + CY macrophages were observed. On day 14 lymphocytic infiltration of the islets was demonstrated only in the groups of mice injected with STZ, STZ + CY while in the group treated with the combination STZ + CY + NSP no infiltration was seen. All experimental groups showed no biochemical evidence for hyperglycemia probably due to the mild destruction of a small number of B cells. The results indicate that NSP might possess a restorative action on insulitis induced by multiple low dose streptozotocin administration in mice.     

Morphological changes of human neuroblastoma cells induced by human gamma interferon

The treatment of GOTO cells, originated from human neuroblastoma, with recombinant human interferon-gamma (rHuIFN-gamma) induced the morphological changes: the extension and bifurcation of neurites and the multinucleated giant cell formation. The treatment of KP-N-RT cells, originated from human neuroblastoma, with rHuIFN-gamma also induced the similar morphological changes. The treatment of these cells with natural HuIFN-gamma also induced the same morphological changes, but those with recombinant human leukocyte interferon (rHuIFN-alpha A), recombinant human fibroblast interferon (rHuIFN-beta) and recombinant murine interferon-gamma (rMuIFN-gamma) did not induce it. The rHuIFN-gamma and the rHuIFN-beta inhibited more strongly the growth of GOTO and KP-N-RT cells than the rHuIFN-alpha A. This suggests that the morphological changes of these neuroblastoma cells are not simply due to the cell growth inhibition, but due to the property which only the rHuIFN-gamma possesses.     

Morphological characteristics of the endocrine pancreas in alloxan diabetes after cyclosporin A administration.

Histological, immunocytochemical, morphometric and electron microscope studies were carried out on the pancreas of alloxan diabetic rats pretreated with cyclosporin A. High mortality, severe destruction of pancreatic B-cells and presence of sporadic mononuclear infiltrations in islets and around excretory ducts were observed. The results obtained show that cyclosporin A potentiates the toxic effect of alloxan on the pancreatic B-cells.     

Morphological changes induced in fungi by antibiotics

In tests of 31 antibiotics, 29 inhibited growth ofBotrytis cinerea and of these, 18 induced morphological changes. Terminal and lateral branching of the hyphae was induced by actinomycin D, aspergillic acid, citrinin, cyanein, cycloheximide, desertomycin and polyene antibiotics. Curling of the hyphae was induced by griseofulvin and narrowing of the hyphae by citrinin. Some antibiotics at different concentrations produced several types of morphological changes. For example, aspergillic acid, desertomycin and flavofungin also induced terminal bulging of the hyphae. Growth of the dimorphic fungusPaecilomyces viridis was inhibited by 24 antibioties, nine of which induced morphological changes. Branching of the hyphae was induced by azalomycin F, citrinin, eyanein, desertomycin, patulin, rugulosin and trichothecin. Griseofulvin had a curling effect. Except for rugulosin, the above antibiotics, in higher concentrations, induced yeast-like growth ofPaecilomyces viridis. Morphological changes were also induced by inhibitors of RNA and protein synthesis and by antibiotics injuring the cell membranes. Antibiotics with different mechanisms of action induced similar morphological changes.     

Morphological changes induced by ampicillin in Campylobacter

Morphologic changes in Campylobacter fetus ssp. jejuni were evaluated as cultivated on thioglycollute broth, containing minimum of 0.1, 1.3 and 10 Ampicillin minimal inhibitory concentration (MIC). During the first four hours of incubation, no changes occurred in the presence of 0.1 MIC; but with the rest of the ampicillin doses, even at the first hour, a proportion larger than 5% of filament-policurved forms was found, and it increased with the incubation time. The greatest number of altered bacteria was found with the use of 10 MIC. No other morphologic changes were observed.     

Morphological changes induced in mouse mammary gland by porcine and human relaxin

The effects of pure porcine relaxin and of human decidual extracts with relaxin-like activity on the mammary gland of virgin mice primed with estrogen have been studied by the light microscope. Porcine relaxin enhanced the changes induced by estrogen alone; the effect was different in the various mammary tissues. In the stroma, relaxin only slightly increased the loosening of connective tissue, the extent of the adipose tissue and of the capillary bed, as well as the degranulation of the mast cells. The changes in the parenchyma, such as elongation and branching of ducts, are strikingly enhanced. Moreover, relaxin seems to promote differentiation of the cells forming the walls of distal ducts, and of the myoepithelial cells. Tissue extracts of human decidua with relaxin-like activity induce changes in the mammary gland similar to those due to porcine relaxin. Such data indicate that relaxin synergizes with estrogen to cause growth of ducts of the mammary gland and that tissue extracts of human decidua have a similar effect, thus providing further evidence that decidua may be a source of relaxin in humans.     

Somatostatin inhibits insulin and glucagon release by monolayer cell cultures of rat endocrine pancreas

Dihydrosomatostatin (0.001–1.0 ug/ml) inhibited both insulin and glucagon secretion by monolayer cell cultures of newborn rat pancreas. When cultures were incubated with somatostatin and then rinsed, the effect of somatostatin appeared to last longer on the pancreatic alpha cell than on the beta cell as indicated by a more prolonged inhibition of glucagon secretion than of insulin release. Submaximal inhibition of glucose-stimulated insulin release by somatostatin was partially reversed by increasing the concentration of glucose. We conclude that the effect of somatostatin appears to be mediated directly on the pancreatic endocrine cells.     

Morphological and biochemical changes in human fibroblast lines induced by anthracyclines during apoptosis

We show that treating human trisomic fibroblasts with anthracyclines - aclarubicin, daunorubicin and idarubicin - leads to certain changes in these cells; namely the activation of caspase 3, morphological changes and an increase in the level of intracellular calcium. These results suggest that anthracycline drugs are also able to induce apoptosis in pathological, trisomic cells.     

Morphological changes in erythrocytes induced by malarial parasites

Host cell alterations induced by Plasmodium falciparum, P. brasilianum, P. vivax and P. malariae were described by electron microscopy and post-embedding immunoelectron microscopy. P. falciparum infection induces knobs, electron-dense material and clefts in the erythrocyte. Clefts are involved in exporting P. falciparum antigen from the parasite to the erythrocyte membrane. P. falciparum antigen is present in knobs which adhere to endothelial cells causing the blockage of cerebral capillaries and ensuing pathological changes in cerebral tissues. P. brasilianum infection induces knobs, short and long clefts and electron-dense material. These structures appear to contain different P. brasilianum antigens. This indicates that each structure functions independently in trafficking P. brasilianum protein to the erythrocyte surface. P. vivax infection induces caveola-vesicle complexes and clefts in the erythrocyte. These structures are also involved in trafficking P. vivax protein from the parasite to the erythrocyte membrane. P. malariae induces caveolae, electron-dense material, vesicles, clefts and knobs in the erythrocyte. Although vesicles and caveolae are seen in the erythrocyte cytoplasm, they do not form caveola-vesicle complexes as seen in P. vivax-infected erythrocytes. They also appear to be involved in trafficking of malaria antigens. These studies, therefore, indicate that host cell changes occur in order to facilitate the transport of malarial antigens to the host cell membrane. The significance of these phenomena is still not clear.     

Effects of porcine diazepam-binding inhibitor on insulin and glucagon secretion in vitro from the rat endocrine pancreas.

Porcine diazepam-binding inhibitor (pDBI) is a novel peptide that has been isolated from the small bowel of the pig, and that occurs also in the islet D-cells. We have studied its effects on hormone release in vitro from the endocrine pancreas of the rat. In isolated islets, pDBI (10(-9)-10(-6)M) did not affect basal insulin release at 3.3 mM glucose, whereas stimulated release at 8.3 mM glucose was dose-dependently suppressed by 32-69% (P less than 0.01). Furthermore, insulin secretion stimulated by either 16.7 mM glucose or 1 mM IBMX (3-isobutyl-1-methylxanthine) or 1 micrograms/ml glibenclamide was suppressed by pDBI at 10(-8) M (by 28-30%, P less than 0.05) and 10(-7) M (by 43-47%, P less than 0.01). In contrast, islet insulin secretion induced by 20 mM arginine was unaffected by these concentrations of pDBI. In the perfused rat pancreas, pDBI (10(-8) M) enhanced by 30% (P less than 0.05) the first phase (0-5 min) of arginine-stimulated insulin release, whereas the second phase (5-20 min) was unchanged. Moreover, pDBI suppressed by 28% (P less than 0.05) the second phase of arginine-induced glucagon release. Arginine-induced somatostatin release was not significantly affected by the peptide. Since pDBI immunoreactivity has been localized also to islet D-cells, the present results suggest that pDBI may act as a local modulator of islet hormone release.     

FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to theDrosophila homeotic proteinsdelta andnotch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation.     

Pathology of the endocrine pancreas.

An immunocytochemical analysis of 94 pancreatic endocrine tumors revealed that 73 tumors were multicellular. Significant amounts of somatostatin and human pancreatic polypeptide were found by radioimmunoassay in extracts of 19 and 17 tumors resp., in addition to the hormone causing the clinical syndrome. Numerous tumors contained ductular structures. In the surrounding pancreatic parenchyma a proliferation of small ducts and budding-off from the ductular epithelium of endocrine cells was often observed. These features are hallmarks of nesidioblastosis of the endocrine pancreas which is a hyperplasia. In multiple endocrine neoplasia I hyperplasia of the endocrine pancreas is combined with larger nodules, currently labeled tumors. On the basis of these findings it is conceivable that pancreatic endocrine tumors are not primarily neoplastic and autonomous but that they are rather of hyperplastic origin.     

Morphological changes in asymmetric erythrocyte membranes induced by electrolytes

Washed human erythrocyte membranes are made permanently leaky to cations by EDTA. These ghosts can exhibit the stomatocyte-disc-echinocyte sequence of shape changes in response to electrolytes in the medium. The changes are instantaneous and reversible. The observations can be explained on the basis of the known effects of cations on charged phospholipids together with the bilayer couple hypothesis.