干细胞向甲状旁腺细胞的分化及在甲状旁腺功能减退中的研究进展

干细胞是一类能够自我复制、自我更新,具有多向分化潜能,能产生多种分化细胞类型的细胞,由于它的自我复制和多向分化潜能,干细胞技术已经被广泛的应用于细胞移植治疗中。甲状旁腺功能减退作为一种内分泌疾病,目前的治疗方案都不能从根本上治疗该疾病。因此应用干细胞来源的甲状旁腺细胞移植治疗甲状旁腺功能减退越来越受到医学界的重视。目前,已有科研团队报道了应用胚胎干细胞（ESCs）、胸腺上皮细胞和扁桃体间充质细胞向甲状旁腺细胞分化及其在甲状旁腺功能减退中的治疗。本文将干细胞向甲状旁腺细胞的分化及在甲状旁腺功能减退治疗中的研究进展进行综述。     

白鱀豚甲状腺及甲状旁腺的初步研究

本文是8头白鱀豚(Lipotes vexillifer)的甲状腺及甲状旁腺的初步研究结果。白鱀豚甲状腺的解剖学和组织学结构与其它海豚相似。其甲状腺滤泡呈圆形或椭圆形,滤泡胶质嗜酸性,滤泡平均直径为106.4微米,滤泡上皮平均高为9.4微米,滤泡旁细胞平均直径为11.0微米。甲状旁腺分布在甲状腺的腹侧面或前、后方,其上皮细胞被结缔组织分隔成团索状。文中并讨论了白鱀豚甲状腺的一些组织形态变化。       

白鱀豚甲状腺及甲状旁腺的初步研究

本文是8头白鱀豚(Lipotes uexillifer)的甲状腺及甲状旁腺的初步研究结果。白鱀豚甲状腺的解剖学和组织学结构与其它海豚相似。其甲状腺滤泡呈圆形或椭圆形,滤泡胶质嗜酸性,滤泡平均直径为106．4微米,滤泡上皮平均高为9．4微米,滤泡旁细胞平均直径为11．0微米。甲状旁腺分布在甲状腺的腹侧面或前、后方,其上皮细胞被结缔组织分隔成团索状。文中并讨论了白鱀豚甲状腺的一些组织形态变化。     

甲氰咪胍能刺激降钙素释放

甲氰咪胍(cimetioine)是一种组织胺H_2受体拮抗剂,用于治疗胃液分泌过多。最近,一些实验提示,甲氰咪胍能抑制甲状旁腺激素(PTH)的分泌以及甲状旁腺组织中cAMP的产生。给正常人或病人用甲氰咪胍,能使血清中PTH的免疫反应降低。作者实验室进一步观察了甲氰咪胍是否也影响降钙素(CT)的释放。从幼年大鼠制备甲状腺-甲状旁腺复合体,在病人手术时得到甲状腺髓样癌组织,将适量组织放于Eagle氏液中,在37℃孵育。药物直接加入孵育液中。分别用特异的放射免疫分析法测定孵育液中的PTH和CT。结果发现,向大鼠的甲状腺-甲状旁腺复合体的孵育液中加入甲氰咪胍,PTH的分泌明显受抑制,而孵育液中的CT明显增加。甲氰咪胍也明显地刺激人甲状腺髓样癌组织释放CT。但是,组织胺或五肽胃素对人甲状腺髓样癌组织释放CT无任何影响。H_1受体阻断剂也不能刺激大鼠甲状腺C细胞释放CT。作者实验室首次报道了甲氰咪胍能直接作用于离体的大鼠和人的C细胞,刺激CT释放。当然,这种作用是否确实通过H_2受体以及其生理意义都有待阐明。     

硒对H2O2诱导的人甲状腺细胞凋亡和超微结构改变的影响

目的：观察硒对H2O2诱导的人甲状腺上皮细胞凋亡和超微结构改变的影响。方法：取良性甲状腺腺瘤旁正常组织进行细胞培养。加硒（10^-7mol／L）或不加硒后加入不同浓度H2O2（0～800μmol／L）刺激单层培养的甲状腺细胞,流式细胞术（FCM）检测甲状腺细胞凋亡率并在电镜下观察其超微结构的改变.结果：经过H2O2作用24h的人甲状腺细胞,随H2O2浓度升高,细胞凋亡率逐渐升高;电镜下甲状腺细胞超微结构呈损伤型改变,甚至出现凋亡、死亡。预先加入10^-7mol／L硒可降低细胞凋亡率,可明显减轻亚细胞结构损伤。结论：硒可减轻H2O2诱发的人甲状腺细胞的氧化损伤,拮抗其导致的细胞凋亡。     

促甲状腺激素对甲状腺细胞胞内游离钙和钙调蛋白的影响

本文研究TSH和forskolin对原代培养的猪甲状腺细胞[Ca~(2+)]_i和钙调蛋白的影响。结果表明,TSH可引起甲状腺细胞[Ca~(2+)]_1急性升高。此反应是剂量依赖关系,而与细胞外钙的存在与否无关。其反应性在细胞单层高于细胞是液,近汇合细胞单层高于汇合细胞单层。TSH作用3天,可使甲状腺细胞的钙调蛋白含量增高,此作用与TSH对甲状腺细胞数的影响无关。Forskolin对甲状腺细胞的[Ca~(2+)]_i和钙调蛋白均无明显的影响。     

金丝猴(Rhinopithecus)甲状腺的C细胞

本文以HE和镀银显示法研究了三种金丝猴甲状腺C细胞的形态与分布。结果表明,金丝猴的C细胞为圆形或椭圆形,主要分布在甲状腺外侧叶上1/3偏内侧的深部,在下1/3外侧缘浅表面也有少量细胞分布。细胞数量少,分布范围窄,主要位于滤泡内和滤泡之间,以单个细胞分布为主,但在滤泡之间偶尔见到有2—3个细胞在一起的。其他部位未见C细胞。三种金丝猴C细胞的形态、数量和分布无明显差异。     

雌激素和孕激素对雌性小鼠甲状腺C细胞的影响

探讨降钙素在老年女性骨质疏松症发病中的作用 ,观察了雌、孕激素对雌性小鼠甲状腺 C细胞的影响。去卵巢小鼠 (OVX)分别肌肉注射苯甲酸雌二醇 (FB)、己烯孕酮 (HPC)和苯甲酸雌二醇加乙烯孕酮 (EB+HPC)两个月。用药剂量根据小鼠口龄和体重的不同而不同。采用免疫组织化学方法显示降钙素 (CT)阳性细胞并对其进行细胞形态计量学分析。结果显示 :(1)去卵巢小鼠与正常对照组相比 ,甲状腺 C细胞数目剧增 ,给予 EB、HPC、EB+HPC治疗的各组小鼠甲状腺C细胞数目与正常对照组水平相近。 (2 )各组小鼠甲状腺 C细胞的大小无明显改变 ,平均直径间无显著性差异 (P>0 .0 5 )。雌、孕激素缺乏可引起雌性小鼠甲状腺 C细胞增生。 C细胞增生也可能是雌激素缺乏引起的骨质疏松的后果     

细胞质膜上的Ca^2＋受体

以前就有过设想；甲状旁腺细胞表面的Ｃａ＾２＋受体可感受细胞外Ｃａ＾２＋浓度变化并起应答反应。最近克隆到的与Ｇ蛋白偶联的Ｃａ＾２＋受体证实了上述观点。Ｃａ＾２＋受体可调节不同细胞活性。Ｃａ＾２＋受体的发现为新药设计提供了新的靶分子物质。     

甲状腺素及维甲酸对成骨样细胞甲状旁腺素受体的调节作用

研究了甲状腺素及维甲酸夺大鼠成骨样细胞ＲＯＳ１７／２．８细胞株甲状旁腺素受体的调节作用实验结果表明：细胞经Ｔ３／Ｔ４处理后,可显增高ＰＴＨ受体结合率及碱性磷酸酶活性,以及ＰＴＨ受体ｍＲＮＡ的表达,细胞经ＲＡ处理后,则相反地降低了ＰＴＨ受体结合率及碱性磷到酶活性。     

THE CYTOLOGY OF THE NORMAL PARATHYROID GLANDS OF MAN AND VIRGINIA DEER : A Light and Electron Microscopic Study with Morphologic Evidence of Secretory Activity

The normal parathyroids of six humans and a Virginia deer were studied by light and electron microscopy. The parenchyma of the deer parathyroid is composed of uniform chief cells, which contained 100 to 400 mµ electron-opaque, membrane-limited granules, presumed to be secretory granules, in addition to the usual cytoplasmic organelles. Desmosomes are present between adjacent cells, and rare cilia are observed protruding from the chief cells into the intercellular space. The human parathyroids contain chief cells in two phases—active and inactive—as well as oxyphil cells. Active chief cells have a large Golgi apparatus, sparse glycogen, numerous secretory granules, and rare cilia. Inactive chief cells contain a small Golgi apparatus, abundant glycogen, and few secretory granules. Both forms have the usual cytoplasmic organelles and, between adjacent cells, desmosomes. Oxyphil cell cytoplasm is composed of tightly packed mitochondria and glycogen granules, with rare secretory granules. Cells with cytoplasmic characteristics intermediate between chief and oxyphil cells, possibly representing transitional cells, have been observed. Secretory granules of both man and deer are composed of 100 to 200 A particles and short rods, and the granules develop from prosecretory granules in the Golgi region of the cell. The human secretory granules are smaller and more variable in shape than those of the deer. The granules are iron and chrome alum hematoxylin-positive, argyrophilic, and aldehyde fuchsin-positive, permitting light microscopic identification. They are also found in the capillary endothelial cells of the parathyroid and in its surrounding connective tissue. The secretory granules of the parathyroid cells can thus be followed from their formation in the Golgi apparatus almost to their extrusion into the blood stream.     

Evidence of the occurrence of calcitonin cells in the ultimobranchial follicle of the rat postnatal thyroid.

A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5-day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells.     

Occurrence of oxyphil cells in suppressed parathyroid glands

Parathyroid glands from Mongolian gerbils cultured for 7 days at a high calcium concentration and examined by electron microscopy, were found to contain suppressed chief cells containing numerous mitochondria, and some oxyphil cells containing an abundance of medium-sized or large mitochondria with calcium-containing precipitates. It is suggested that parathyroid chief cells may be transformed into oxyphil cells, under certain conditions, and that the associated increase in the number and size of the mitochondria may be related to an intracellular accumulation of calcium.     

The fine structure of the parathyroid gland

The fine structure of the parathyroid of the macaque is described, and is correlated with classical parathyroid cytology as seen in the light microscope. The two parenchymal cell types, the chief cells and the oxyphil cells, have been recognized in electron micrographs. The chief cells contain within their cytoplasm mitochondria, endoplasmic reticulum, and Golgi bodies similar to those found in other endocrine tissues as well as frequent PAS-positive granules. The juxtanuclear body of the light microscopists is identified with stacks of parallel lamellar elements of the endoplasmic reticulum of the ergastoplasmic or granular type. Oxyphil cells are characterized by juxtanuclear bodies and by numerous mitochondria found throughout their cytoplasm. Puzzling lamellar whorls are described in the cytoplasm of some oxyphil cells. The endothelium of parathyroid capillaries is extremely thin in some areas and contains numerous fenestrations as well as an extensive system of vesicles. The possible significance of these structures is discussed. The connective tissue elements found in the perivascular spaces of macaque parathyroid are described.     

Adrenomedullin immunoreactivity tissue distribution in parathyroids of the patients with primary hyperparathyroidism.

Adrenomedullin (ADM) is a new potent vasorelaxant peptide identified originally in extracts of pheochromocytoma, and is widely distributed within the tissue. Although histopathological studies have demonstrated the presence of ADM-immunoreactivity (ir-ADM) in some human neuroendocrine tumors (such as insulinoma, pituitary adenoma, and gastrointestinal neuroendocrine tumors), data on the presence of ADM in normal and pathological parathyroid gland are not available. Plasma AM concentrations were recently reported to be elevated in patients with PHP (primary hyperparathyroidism). The aim of our study was to determine tissue distribution of ir-AM in 34 patients with PHP (27 female and 7 male, mean age 50 +/- 6 years) undergoing surgery. Six normal parathyroid samples incidentally found during thyroidectomy for neoplastic diseases and ten sections of human rectus abdominis muscle tissue were used as controls (C). Adenomatous parathyroids were found in 22 PHP and hyperplastic parathyroids in twelve PHP patients. Four hyperplastic parathyroids were found in three PHP patients and three parathyroids in 10 PHP patients. Eight parathyroids revealed a prevalent diffuse growth pattern and four showed a prevalent nodular growth pattern. Immunohistochemical ADM expression was seen in seven of twelve (58.3 %) hyperplastic parathyroids and in fourteen of twenty-two (66.6 %) adenomatous glands. Parathyroid chief cells showed strong cytoplasmatic staining, whereas oncocytic cells showed a faintly aspecific cytoplasmatic staining. Normal parathyroids were negative for ir-ADM. In conclusion, we found the presence of ADM in parathyroid chief cells of PHP patients using immunohistochemistry in our study.     

Are Stannius corpuscles the parathyroid glands of teleost fishes? Ultrastructural, cytologic and immunocytochemical arguments

Parathyrin of Stannius corpuscles (PCS), glands which are restricted to Holostei and Teleostei, is closely related to mammalian parathyrin (PTH) secreted by the parathyroids [( 6] to [9]). In unstimulated and stimulated CS we have shown the same structure and cellular types that are described in mammalian parathyroids. We observed three types of cells; the two sorts of cells already described [14] present such a difference of density (Fig. 1) that type I may be compared to chief dark cells and type II to chief light cells. The difference between these two forms was particularly marked in activated CS; a similar observation has been reported concerning PT [15]. Furthermore, we have detected a third type of cell present either singly in unactivated CS or in small groups between chief cells in activated CS. They showed all the characteristics of oxyphil cells [17]; they present an extremely dense cytoplasm with numerous mitochondria and a typical stellate form with cytoplasmic processes extending between chief cells (Figs. 2, 3). In CS of untreated eels, we have shown by means of indirect immunocytology (using an immunserum raised against the active fragment 1-34 bPTH) that the immunostained reaction product was limited to dilated cisternae and ribosomes of the rough endoplasmic reticulum and to most of the granules in all the chief cells (Figs. 4, 5). No immunoreaction was observed in Golgi area. Oxyphil cells did not present an immune localization of PCS. CS are structurally and cytologically similar to mammalian PT; furthermore their chief cells synthesize, stock and secrete a substance immunologically similar to mammalian PTH; the exact function of oxyphil cells has to be demonstrated.     

Innervation of the parathyroid in the european starling (Sturnus vulgaris)

Anatomical studies were conducted to characterize the source, type, and distribution of parathyroid gland innervation in European starlings. Denervation experiments demonstrated that the parathyroid glands and adjacent carotid bodies are innervated by nerve fibers originating in the nodose ganglion of the vagus nerve. In the parathyroid parenchyma, these fibers terminate adjacent to chief cells or near vascular smooth muscle. Vagal fibers also form synapses with catecholamine-containing glomus cells of the carotid body. Blood that first perfuses the carotid body subsequently perfuses the parathyroid parenchyma. These observations suggest that vagal innervation may influence parathyroid function in starlings either through direct chief cell innervation or through alteration of vascular perfusion. A neurohemal relationship also may exist between the carotid body and parathyroids.     

Calcitonin cells and unusual follicles of the thyroid of the indian grey mongoose, Herpestes edwardsi (Geoffroy).

Histological preparations of thyroid, parathyroid and thymus glands of Herpestes edwardsi were examined for calcitonin cells. They reveal that (1) the thyroid calcitonin cells are oval, rounded and rarely elongated in shape; these cells and their nuclei are distinctly larger than those of the follicular cells and their nuclei; (2) calcitonin cells are unevenly distributed in the thyroid, with the result that certain portions of the thyroid are completely devoid of these cells; (3) on an average, calcitonin cells are in a ratio of 10-15 cells/100 follicular cells; (4) the parathyroid and thymus glands do not display calcitonin cells, and (5) the thyroid gland displays unusual follicles of two categories, (a) follicles with ciliated epithelial cells and (b) follicles with squamous epithelium.