Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica

A pituitary tumour composed of well-differentiated corticotrophs and adrenocortical cells is reported. Sections of the tumour revealed a mixture of small round cells with amphophilic or basophilic periodic acid-Schiff (PAS)-positive cytoplasm and large spherical and oval cells with abundant, granular, partly vacuolated PAS-negative cytoplasm. The small cells contained type 1 cytokeratin-positive microfilaments, numerous 250–500 nm endocrine-type secretory granules immunoreactive for adenocorticotropic hormone (ACTH) and -lipotropin. The large cells possessed ample cytoplasm filled with abundant vesicular smooth endoplasmic reticulum, numerous mitochondria possessing tubulovesicular cristae and frequent dense bodies. They lacked the features of pituitary endocrine cells or folliculostellate cells and were found to contain a panel of steroidogenic dehydrogenases and hydroxylases. The tumour was classified as a choristoma, in which two distinct cells types, corticotrophs and adrenocortical cells, were mixed. We suggest that, under continued ACTH stimulation, uncommitted stem cells may differentiate into adrenocortical cells. Alternatively, the presence of adrenocortical cells may be the result of heterotopia.     

Pituitary Folliculo-Stellate-Like Cells Stimulate Somatotroic Pituitary Tumor Growth in Nude Mice

A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation, MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude mice. In contrast all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors.     

Age-related accumulation of congophilic fibrillar inclusions in endocrine cells

Summary Intracellular fibrillar congophilic inclusions are well known as neurofibrillary tangles in neurons and as Biondi bodies in choroid plexus epithelial cells. Recently similar amyloid-like inclusions in adrenal cortical cells were described (Eriksson and Westermark 1990). This study on 150 adrenal glands confirms these observations. In our material the age-related accumulation of congophilic inclusions starts earlier (in the sixth decade) and reaches a higher incidence (42.7%). We found similar intracellular inclusions in other endocrine organs, for example in the anterior lobe of the pituitary, in the cells of parathyroid glands and in Sertoli cells. The age-related incidence of these fibrillar inclusions in the pituitary was 68%; the co-incidence with interstitial amyloid deposits was 49.5%. Thus the intracellular accumulation of congophilic fibrils in old age is a widespread phenomenon and occurs not only in neurons but also in endocrine cells (adrenal, pituitary and parathyroid glands) and in active secretory cells (choroid plexus and Sertoli cells).     

大鼠下丘脑及邻近区域催产素免疫阳性神经元与垂体后叶的关系

本文运用免疫细胞化学PAP及ABC法,显示大白鼠下丘脑内OXT免疫阳性神经元,并于垂体后叶注射WGA-HRP,显示下丘脑中逆行标记细胞,结合免疫细胞化学方法,观察下丘脑及其邻近区域内HRP与OXT双标记细胞,证实下丘脑视上核、室旁核、穹窿前核和后核、血管周细胞群、下丘脑视前区、下丘脑前区及外侧区、背侧副细胞群内、室周部、第三脑室侧壁室管膜细胞下及室间孔部室管膜细胞下,均有OXT免疫阳性神经元,其中至少部分神经元可发出向垂体后叶的投射纤维。位于第三脑室侧壁室管膜下及室间孔部室管膜下的神经元,可能监测脑脊液中各种因素的变化,调节垂体后叶OXT的分泌,也可能直接通过共树突向脑脊液内释放OXT。     

Immunocytochemical detection of effects of TRH and T4 on prolactin- and TSH-producing cells in the pituitary gland of Rana ridibunda

Effects of synthetic thyrotropin-releasing hormone (TRH) and various doses of thyroxin (T4) on prolactin (PRL)-producing cells and thyrotropic cells in the pituitary were investigated in adult male and female Rana ridibunda frogs. Animals were given 200 microg TRH once a week for 4 weeks and 0.2-0.5 mg T4 during 3 days per week for a period of 2 weeks by injections in the groin. PRL-producing cells and thyrotropic cells were identified with light microscopical and electron microscopical immunocytochemical methods, using rabbit anti-PRL and rabbit anti-thyroid stimulating hormone (TSH) as primary antibodies. TRH caused cytological changes in both cell types, which were consistent with increased synthesis and release of both PRL and TSH. Treatment with 0.5 mg T4 activated both cell types less than TRH treatment did, whereas 0.2 and 0.4 mg T4 caused inactivation of both cell types. In conclusion, mammalian TRH is effective on both types of frog pituitary cells. Our study suggests that T4 has a positive rather than a negative effect when concentrations above a certain threshold are given.     

Stability of intracranial self-stimulation following hypophysectomy

The possibility of a hypothalamo-pituitary involvement in the intracranial self-stimulation phenomenon was investigated. Threshold and optimal stimulation currents were identified by means of the method of limits, in rats with bipolar electrodes implanted in the lateral hypothalamus. Total or sham hypophysectomies were performed after the establishment of these current values, and found to have no effect on reinforcing brain stimulation. It was concluded that a hypothalamo-pituitary mechanism does not subserve reinforcing brain stimulation.     

Pituitary chromophobe adenomas consisting of prolactin cells

Summary Morphologic studies of pituitary neoplasms removed by surgery from 36 human patients revealed 8 chromophobe adenomas which differed clearly from the remaining tumors. The cytoplasm of the adenoma cells failed to stain with PAS, aniline blue, aldehyde fuchsin, aldehyde thionin, orange G or light green, but positively stained granules were found by using erythrosine or carmoisine. Immunoperoxidase technique disclosed the presence of prolactin in the cytoplasm of some adenoma cells. The adenoma cells exhibited distinct ultrastructural features such as well developed rough surfaced endoplasmic reticulum with Nebenkern formation, prominence of Golgi apparatus, presence of misplaced exocytosis as well as pleomorphism of secretory granules with a considerable variation of size ranging from 130 to 500 nm in diameter. Thus, by electron microscopy the adenoma cells showed a close resemblance to prolactin cells of the non-tumorous pituitary glands except for the reduced size and number of secretory granules.These chromophobe adenomas are regarded as representing a distinct pathological entity clearly distinguishable from other forms of pituitary neoplasms. In view of the morphologic findings and the elevation of blood prolactin level (measured in 3 patients) the term, sparsely granulated prolactin producing pituitary adenoma, appears to be the most appropriate one to designate these tumors.The authors wish to thank Dr. H. Friesen for providing the anti-human prolactin and Dr. L. A. Sternberger for the peroxidase-anti-peroxidase complex. The excellent technical assistance of Mrs. Gezina Ilse and Miss Nancy Macphail and the valuable secretarial help of Mrs. Maureen Rowling are appreciated.The work was supported in part by MA-552 grant of the Medical Research Council of Canada and by the St. Michael's Hospital Research Society.     

Immunohistochemistry of folliculo-stellate cells in normal human adenohypophyses and in pituitary adenomas

Summary Presence and distribution of S-100 protein (S-100), neuron-specific enolase (NSE), cytokeratin polypeptides, glial fibrillary acidic protein (GFAP), vimentin, actin, lysozyme and pituitary hormones (prolactin, hGH, ACTH, -FSH, -LH, -TSH, alpha subunit) in folliculo-stellate cells (FSC) were studied in seven normal human pituitary glands and 28 pituitary adenomas using peroxidase-antiperoxidase and the avidin-biotin immunohistochemical techniques. Approximately 5% of the cells of the adenohypophysis were agranular, non-hormon-producing FSC most of which showed a conspicuous and strong reaction with S-100 antibodies but some were, in addition, GFAP- and vimentin-positive. In contrast to endocrine cells (EC), FSC were not decorated by antibodies to NSE or cytokeratins. In addition to supportive functions, these cells, due to their close special relationship to EC, seem to have transport and other metabolic functions yet to be elucidated. By their S-100 reactivity and their distribution FSC are comparable to glial cells of the central and schwann and satellite cells of the peripheral nervous system (PNS) as well as to supportive cells in neuroendocrine organs and related tumors (e.g., pheochromocytomas, paragangliomas, carcinoids). With one exception, S-100 reactive FSC were not found in pituitary adenomas. The immunohistochemical demonstration of S-100 protein in pituitary tissue is, therefore, a reliable aid in the discrimination between adenomas and normal pituitary tissue, particularly in small and poorly preserved specimens. In one adenoma FSC were found in addition to ACTH-producing tumor cells. This seems to be an extremely rare event suggesting a combination tumor.Supported in part by Fonds zur Förderung der wissenschaftlichen Forschung (no. 4708) to H. Denk     

吡啶斯的明试验对评价垂体hGH储备功能的价值

垂体hGH分泌受中枢神经介质调控。兴奋胆碱能系统可使hGH增加。本文试用胆碱酯酶抑制剂吡啶斯的明兴奋hGH,并与胰岛素兴奋试验进行比较,观察了13名正常青少年和10名垂体性侏儒症患者对两种兴奋试验的反应。结果显示口服吡啶斯的明2mg/kg体重能迅速有效地兴奋垂体hGH释放。其作用较胰岛素兴奋试验更强,是一项值得推荐的判定青少年垂体hGH储备功能的试验。     

Immunohistochemical Heterogeneity Within Clinically Nonfunctioning Pituitary Adenomas

To investigate whether adenohypophysial hormone expression is heterogeneous within individual clinically nonfunctioning pituitary adenomas, immunohistochemical examinations were performed on tissues obtained by multiple sampling of 11 adenomas. Stained sections were assessed by morphometric image analysis as well as semiquantitative estimation under microscopy. All tumors except one were immunopositive for one or more gonadotropins. Results were divided into five grades based on the proportion of immunoreactive cells per section. Semiquantitative estimation showed only a one-grade difference among samples from the same tumor in four cases for FSHβ and in two cases for LHβ. These qualitative similarities between multiple samples were confirmed by morphometric image analysis. From the practical standpoint of making a diagnosis of nonfunctioning pituitary adenoma, it is not necessary to take into account immunohistochemical heterogeneity within an individual tumor, and immunohistochemical findings in a given sample obtained at surgery can be regarded as representative of the entire adenoma.