Ultrastructural observations on the mechanism of secretion in the rat parathyroid after fluoride ingestion

Summary The secretory mechanism of the parathyroid glands of fluoride treated rats is evaluated ultrastructurally and compared to that of control rats. The principal difference between the two groups of rats concerns the rate of activity of the chief cells of the gland. In the control animals, these cells are predominantly inactive. In the fluoride-treated rats, they exhibit a more active stage of the secretory cycle. The active chief cells in rats treated with fluoride contain increased numbers of secretory granules. These granules are released into the perivascular spaces within cytoplasmic projections suggesting an apocrine-like mechanism for the secretion of parathyroid hormone. Secretory granules are observed free in the perivascular spaces and within the cytoplasm of capillary endothelial cells in the parathyroid glands.     

Mating modifies apoptosis pattern in epithelial cells of the rat uterus

Estrous cycle in mammals includes marked epithelial changes in reproductive tract, regulated by sex steroid hormones. In the present work we studied the activation of caspases and apoptotic pattern in uterine epithelial cells during proestrus and estrus, and the effect of mating in this process. In addition, we investigated the role of seminal vesicle secretions on apoptosis of uterine epithelia. Apoptotic index was evaluated by TUNEL assay, caspases‐8, ‐9, and ‐3 activation was detected by Western blot and active caspase‐3 expression was detected by immunohistochemistry. Our results show that mating during proestrus and estrus transition induced changes in the apoptotic pattern of uterine luminal epithelium during estrus, characterized by a delay in the onset of apoptosis as compared with that observed in nonmated rats. No differences in the apoptotic pattern in the glandular epithelium between mated and nonmated rats were observed. Seminal vesicle secretions inhibited luminal epithelium apoptosis, while no changes in glandular epithelium apoptosis were observed. We also demonstrate that activation of caspases‐8, ‐9, and ‐3 occurred in both mated and nonmated rats. Active caspase‐3 was detected in the luminal and glandular epithelium in both nonmated and mated rats. The overall results indicate that mating delays but does not prevent the cellular death of the rat uterine luminal epithelium and seminal vesicle secretions are involved in this delay. Finally, the activation of both the mitochondrial and the membrane receptor pathways of cell death are implicated in the molecular mechanism of uterine apoptosis. Mol. Reprod. Dev. 76: 564–572, 2009. © 2008 Wiley‐Liss, Inc.     

Parathyroid gland volume increases with postmaturational aging in the rat

To examine the pathophysiology of the age-related rise in the plasma concentration of parathyroid hormone (PTH), we studied the relationships among plasma immunoreactive PTH (iPTH), parathyroid gland volume, parathyroid cell proliferation rate, renal function, and blood Ca(2+) in male Fischer 344 rats aged 6-28 mo. Plasma iPTH increased 2.5-fold between 6 and 28 mo and correlated with parathyroid gland volume (r = 0.87). Gland volume began to increase as early as 6-12 mo of age and by 28 mo was threefold greater than at 6 mo. Gland expansion was a consequence of hyperplasia stimulated in part by an increase in cell proliferative activity late in life. Blood Ca(2+) and plasma inorganic phosphorus did not change significantly with age. Glomerular filtration rate decreased with age but only after the age of 24 mo. Unlike what has been observed in the human, these data suggest that the age-related increase in plasma iPTH in the rat is linked to parathyroid gland hyperplasia and that early gland growth does not appear to be associated with hypocalcemia or renal insufficiency, but rather to developmentally related metabolic changes. Later in life (>24 mo), the increase in parathyroid cell proliferation rate, further hyperplastic expansion of the gland, and increase in iPTH secretion appear to be associated with renal insufficiency.     

Thyroid cryotherapy in an experimental rat model

In recent years cryotherapy has been more and more frequently used for the treatment of tumors of different organs. Until now, the use of cryotherapy for the treatment of thyroid lesions, as well as histopathologic changes in thyroid tissue after cryotherapy, has not been described. Nitrous oxide cryotherapy of one thyroid lobe in twenty 12-week male Wistar rats was performed. After 2 and 4 weeks, the cryotreated thyroid lobe and the second lobe along with a part of the trachea, esophagus, and the subhyoid muscles adhering to the thyroid were excised and assessed macro- and microscopically. The macroscopic evaluation, performed 2 and 4 weeks postcryotherapy, revealed atrophy of the cryotreated lobe in 4 and 3 rats, respectively, and reduction of the cryotreated lobe dimensions in 6 and 7 rats, respectively. In the specimens of the lobes excised 2 weeks following cryotherapy, examined microscopically, necrosis, granulomatous inflammation, hemorrhages, and hemosiderin deposits were found most often, whereas in the specimens of the lobe excised after 4 weeks lymphocytic inflammation and fibrosis were mainly observed. No microscopic changes were observed in the thyroid lobes that were not frozen or in the parathyroid glands located inside these lobes or extrathyroidally, either ipsilaterally or contralaterally to the cryotreated thyroid lobes. There was no microscopic damage to other tissues adjacent to the thyroid gland. No rat developed vocal cord dysfunction after cryotherapy and no significant changes in serum calcium level before and after cryotherapy were observed. The results obtained show that it is possible to cryoblate thyroid tissue without damaging the tissues adjacent to the thyroid, as well as to spare function of the recurrent laryngeal nerves and parathyroid glands.     

Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid cells

Calcimimetic compounds inhibit not only parathyroid hormone (PTH) synthesis and secretion, but also parathyroid cell proliferation. The aim of this investigation is to examine the effect of the calcimimetic compound NPS R-568 (R-568) on parathyroid cell death in uremic rats. Hyperplastic parathyroid glands were obtained from uremic rats (subtotal nephrectomy and high-phosphorus diet), and incubated in the media only or the media which contained high concentration of R-568 (10(-4)M), or 10% cyclodextrin, for 6h. R-568 treatment significantly suppressed medium PTH concentration compared with that of the other two groups. R-568 treatment not only increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay-positive cells, but also induced the morphologic changes of cell death determined by light or electron microscopy. These results suggest that CaR activation by R-568 accelerates parathyroid cell death, probably through an apoptotic mechanism in uremic rats in vitro.     

The influence of a single ethanol injection on normal thyroid tissue of the rat

Macro- and microscopic changes in the normal thyroid gland of rats, and in the surrounding tissues 2 and 4 weeks after a single intrathyroidal ethanol injection (IEI), together with the influence of such treatment on the function of the recurrent laryngeal nerves and of the parathyroid glands, were assessed. The intraoperative macroscopic evaluation at 2 weeks (20 rats) and 4 weeks (20 rats) after IEI revealed the presence of a scar at the site of the IEI-treated lobe in seven (35%) and six (30%) rats, respectively, and the reduction of lobe dimensions in thirteen (65%) and fourteen (70%) rats, respectively. The microscopic evaluation of the lobe after IEI showed coagulative necrosis, reduction in thyroid follicle volume, disturbance of follicle structure, haemorrhage, haemosiderin deposits, inflammatory infiltration and fibrosis. No microscopic changes were observed in the tissues surrounding the thyroid, nor in the parathyroid glands located extrathyroidally or in the second thyroid lobe. No vocal cord dysfunction or significant changes in serum calcium levels after IEI were detected.     

The effects of adrenalectomy on the harderian gland of the Wistar albino rats

Harderian glands of the Wistar albino rats normal and adrenalectomized were investigated by light microscopy. In normal, these glands have a tubuloalveolar structure. The gland is located in the medio posterior aspect of the orbit. It is lobulated and appears homogeneous in colour and texture. Harderian gland consist of tubules with wide lumina lined by a single layer of columnar epithelial cells surrounded by myoepithelial cells within their basal lamina. It contains porphyrin pigment which is stored as solid intraluminal deposits. The glandular epithelium possesses two cell types, termed A and B. Type A cells are more numerous. The single excretory duct of the gland is directly continuous with endpieces at the hilus and opens nasally and ventrally to the third eyelid. The excretory duct is accompanied by many acini of small serous glands around it. The tubuloalveoli of the gland is not divided into lobules. There is no branched duct system within the gland. The secretion seems to be associated with porphyrins, is essentially released by exocytosis, but holocrine secretion also occurs. The single excretory duct is lined by a stratified epithelium. The gland is surrounded by a collagenous capsule. The adrenalectomy, caused degenerative changes in the glands. Epithelial height was lower than in normal gland epithelium. Most of the acini were completely disorganised. The acinar lumina were filled with porphyrin debris. The results suggest that rat harderian glands are sensitive to adrenal androgen changes in both male and female rats.     

Effect of enkephalins on the function of the calcium-regulating endocrine glands in shock

The experiments on white rats weighing 180-220 g have shown that in traumatic and hemorrhagic shock the initial increase in parathyroid hormone blood concentration is followed by the decrease of functional activity of parathyroid glands. Calcitonin concentration is found to increase during the first hours of shock. The changes in calcium-regulating gland function result in significant disturbances of calcium exchange during shock. The injection of synthetic leu-enkephalin analogs to rats with shock leads to normalization of calcium-regulating endocrine glands function.     

Sex dimorphism in the thyroid gland. IV. Cytologic aspects of sex dimorphism in the rat thyroid gland

This study was designed to explain whether the sex-dependent differences in the structure of the thyroid gland of adult male and female rats depend on quantitative or qualitative changes in the thyroid follicular cells. Absolute thyroid gland weight was similar in male and female rats, but its relative weight was markedly higher in females however. Volume fractions of epithelium and stroma were higher and that of colloid lower in male than in female rats and the epithelium/colloid ratio was higher in the males. Also absolute the volumes (in mm3) of epithelium and stroma were higher in the males; the thyroid gland of females contained more colloid. The average volume of a thyroid follicular cell, estimated by stereology, was higher in males than in females, although the thyroid gland contained similar numbers of follicular cells in both sexes. Also, thyroid glands from both male and female rats contained a similar DNA quantity. Results of the present study show that the sex dimorphism in the rat thyroid depends upon a difference in the mean volume of thyroid follicular cells, with males having larger cells than females. However, in both sexes the thyroid gland contains a similar quantity of these cells.     

Ultrastructural changes in rat palatal epithelium after beta-aminopropionitrile.

Beta-Aminopropionitrile (BAPN) retarded or suppressed epithelial changes in the medial edge of the palatal process in later stages of gestation in rats. Programmed cell death did not follow the usual pattern, and only a few lysosomes were observed on day 18 of gestation. The sensitivity of the medial epithelium to BAPN appeared to be different in various areas of the palatal epithelium; the epithelium on the anterior region of the palatal process was hypertrophied and keratinized, while posteriorly the medial or neighboring epithelium was very thin and, in neonatal rats, the covering was absent. A basal lamina was distinct in the anterior region and indistinct or fragmented posteriorly. Collagen fibers did not develop adjacent to the basal lamina, and an amorphous material was scattered throughout the mesenchymal tissue. These findings suggest that BAPN decreases the "connecting capacity" between mesenchyme and epithelium, and results in a modification of epithelial changes.     

Zinc deficiency aggravates tubulointerstitial nephropathy caused by ureteral obstruction

Ureteral ligation causes tubulointerstitial nephropathy characterized by the tubular dilatation, the interstitial expansion, and a leukocyte infiltration into the tubulointerstitium. The present study was designed to explore whether zinc (Zn) deficiency affects the development of unilateral ureteral obstruction (UUO)-induced tubulointerstitial nephropathy. Compared to rats fed a standard diet, rats fed a Zn-deficient diet exhibited a greater influx of leukocytes into the tubulointerstitium of the cortex of the obstructed kidney 3 d following UUO. Furthermore, rats fed a Zn-deficient diet showed a slight invasion of leukocytes into the tubulointerstitium of the cortex of the contralateral nonobstructed kidney (CLK), although there was no infiltration of leukocytes into the CLK of rats fed a standard diet. These histological changes, however, were ameliorated by administration of enalapril, an angiotensin (ANG) I-converting enzyme inhibitor. Thus, it is suggested that Zn deficiency aggravates UUO-induced tubulointerstitial nephropathy via an increase in the action of ANG II.     

大鼠实验性腺胃癌形成过程中脑垂体远侧部ACTH细胞的免疫组织化学观察

用断乳雄性 Wistar大鼠 15只 ,分为实验性胃癌组和盐水对照组。实验性胃癌组大鼠用 MNNG灌胃 ,流式细胞仪测定有异倍体 (10 0 % )后 ,断头处死动物 ,快速取出脑垂体。用免疫组织化学、图像分析和形态计量方法观察大鼠实验性腺胃癌发生过程中脑垂体远侧部 ACTH细胞的变化。结果表明 ,实验性胃癌组大鼠脑垂体远侧部 ACTH阳性细胞的面数密度增大 ,反应增强 ,与对照组相比有显著性差异 (P<0 .0 1,P<0 .0 5 )。结果提示 ,在大鼠实验性腺胃癌发生过程中 ,脑垂体远侧部 ACTH细胞可能参与了机体抗肿瘤的内分泌调节。     

The effects on the male genital organs and dogs of a new antifertility compound KABI 1774

The effects of KABI 1774, a new antifertility compound, on the genital organs of rabbits and dogs were studied by means of electron microscopy. KABI 1774 (2,6-cis-diphenylhexamethylcyclo-tetrasiloxane) was administered daily in a dose of 2 mg/kg body weight to rabbits for 2, 5, 10, 15, 20, 25, and 30 days, and in doses of 10 mg/kg and 250 mg/kg body weights to dogs for 40 days. In rabbits, cell demise was observed in the epididymes, especially in the middle caput and corpus after 2, 5, and 10 days, and was sometimes seen in the accessory gland. After 15 days, spermatozoa in the corpus did not demonstrate normal maturation changes, and after 20 days, spermatozoa in the cauda epididymis were dead. Between 15 and 25 days, the seminiferous tubules showed arrested spermatogenesis, followed by degeneration of all spermatids and many spermatocytes. The epithelium of the pelvic urethra was infiltrated with granulocytes. In dogs, the effects on the seminife rous epithelium ranged from arrested spermatogenesis to complete degeneration of most germ cells. Atrophy of the interstitial cells, shrinkage of the nucleus, and considerable loss of the specialized cytoplasmic ultrastructure were observed. There was some cell death and highly marked atrophy of the epithelium. Generally, no spermatozoa were observed. Marked epithelial atrophy was present in the prostate gland, and a few areas also showed epithelial metaplasia. The findings are con sistent with the concept that the cyclotetrasiloxane compound mimics estrogens in its antigonadotropic effect, though a direct antiandrogenic effect on the epididymes may also be involved.     

Effects of vitamin E and selenium deficiency on the fatty acid composition of rat retinal tissues

The fatty acid composition of retinal tissues was measured in rats maintained for 26–32 weeks on each of the following diets: a purified basal diet deficient in α-tocopherol and selenium, an identical control diet supplemented with α-tocopherol and selenium, and a commercial laboratory rat chow. Dietary deficiencies of antioxidant nutrients were found to cause a large decrease in total polyunsaturated fatty acids in the retinal pigment epithelium, a small decrease in the retinal rod outer segments, but no change in the whole retina or liver when compared to tissues from animals fed the vitamin E- and selenium-supplemented control diet. The polyunsaturated fatty acid content which we have observed for the retinal pigment epithelium from rats fed commercial lab chow is similar to that which we observed for bovine retinal pigment epithelium.Our results indicate that changes in fatty acid composition are not generalized to all tissues in severely antioxidant-deficient animals, but that changes do occur in some tissues, such as the retinal pigment epithelium, which appears to be particularly sensitive to in vivo lipid peroxidation.     

Effects of vitamin E and selenium deficiency on the fatty acid composition of rat retinal tissues.

The fatty acid composition of retinal tissues was measured in rats maintained for 26--32 weeks on each of the following diets: a purified basal diet deficient in alpha-tocopherol and selenium, an identical control diet supplemented with alpha-tocopherol and selenium, and a commerical laboratory rat chow. Dietary deficiencies of antioxidant nutrients were found to cause a large decrease in total polyunsaturated fatty acids in the retinal pigment epithelium, a small decrease in the retinal rod outer segments, but no change in the whole retina or liver when compared to tissues from animals fed the vitamin E- and selenium-supplemented control diet. The polyunsaturated fatty acid content which we have observed for the retinal pigment epithelium from rats fed commerical lab chow is similar to that which we observed for bovine retinal pigment epithelium. Our results indicate that changes in fatty acid composition are not generalized to all tissues in severely antioxidant-deficient animals, but that changes do occur in some tissues, such as the retinal pigment epithelium, which appears to be particularly sensitive to in vivo lipid peroxidation.     

Ultrastructure of the proteoglycan component of the extracellular matrix in the intact mammary gland and in benign and malignant mammary gland tumors

Proteoglycans (PG) were revealed by electron microscopy using cation dyes, Alcian blue and safranin O. In intact mammary gland of dogs, each histogenetic type of cells had its specific features in the ultrastructure of pericellular matrix proteoglycan component. A thin-stitched net, consisting of small PG granules and thin filaments has been observed in the pericellular space of secretory epithelium. A well-proportioned PG net is absent near fibroblasts and macrophages. Net-like PG structure is found in the endothelium, pericytes and adventitial cells of blood capillaries. Visual changes in PG-containing extracellular matrix are observed in the epithelium of mammary gland tumors.     

Effect of insulin therapy on renal changes in spontaneously diabetic Torii rats.

The spontaneously diabetic Torii (SDT) rat has recently been established as an animal model of non-obese type 2 diabetes, in which ocular complications severe occur. However, the function and morphological features of the diabetic renal lesions in SDT rats have not been reported in detail. Therefore, we evaluated changes over time in renal lesions in SDT rats. In addition, SDT rats were treated with insulin to observe whether these renal complications are caused by hyperglycemia. Renal functional parameters and renal lesions were monitored in SDT rats from 8 to 68 weeks of age. Sprague-Dawley (SD) rats of similar age were used as control animals. In the insulin-treated group of SDT rats, insulin pellets were implanted at 24 weeks of age to compare the development of renal lesions. The SDT rats began to develop hyperglycemia at 20 weeks of age. In the histopathological examination of the kidney, glycogen deposition of the renal tubular epithelium and renal tubular dilation were observed from 24 weeks of age in the untreated SDT rats, and the changes in the renal tubules markedly progressed with aging. Moreover, thickening of the glomerular basement membrane was observed from 32 weeks of age. At 50 weeks of age, the glomeruli showed increase of mesangial matrix, with predominantly diffuse lesions showing by 68 weeks of age. The mesangial proliferation gradually progressed. In the SD rats, no renal lesions were present at 50 and 68 weeks of age. SDT rats with insulin treatment remained normoglycemic throughout observation and their renal functional parameters were normal. Glycemic control in SDT rats prevented the development of renal lesions. The features of SDT rats indicate their usefulness as an animal model for investigating diabetic nephropathy.     

Effects of pinealectomy on the ultrastructure of the golden hamster parathyroid gland

Ultrastructural changes of the parathyroid glands of pinealectomized golden hamsters were investigated. The main changes in the parathyroid glands 1 hour and 1 day after pinealectomy compared with the control and sham-operated groups were an increase of the Golgi complexes, cisternae of the granular endoplasmic reticulum and large vacuolar bodies. In addition, many chief cells contained numerous prosecretory granules in the Golgi areas and many secretory granules in the peripheral cytoplasm. The morphology of the parathyroid glands 7 and 30 days after pinealectomy resembled that of the control parathyroid glands. These results suggest that pinealectomy affects the secretory activity of the parathyroid gland.     

Extracellular Ca2+-sensing receptors--an overview

Extracellular Ca2+-sensing receptors (CaRs) are the molecular basis by which specialized cells detect and respond to changes in the extracellular [Ca2+] ([Ca2+]o). CaRs belong to the family C of G-protein coupled receptors (GPCRs). Activation of CaRs triggers signaling pathways that modify numerous cell functions. Multiple ligands regulate the activation of CaRs including multivalent cations, L-amino acids, and changes in ionic strength and pH. CaRs in parathyroid cells play a central role in systemic Ca2+ homeostasis in terrestrial tetrapods. Mutations of the CaR gene in humans cause diseases in which serum and urine [Ca2+] and parathyroid hormone (PTH) levels are altered. CaR homologues are also expressed in organs critical to Ca2+ transport in ancient and modern fish, suggesting that similar receptors may have long been involved in Ca2+ homeostasis in lower vertebrates before parathyroid glands developed in terrestrial vertebrates. CaR mRNA and protein are also expressed in tissues not directly involved in Ca2+ homeostasis. This implies that there may be other biological roles for CaRs. Studies of CaR-knockout mice confirm the importance of CaRs in the parathyroid gland and kidney. The functions of CaRs in tissues other than kidney and parathyroid gland, however, remain to be elucidated.