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Biomedical subjects

N Sanno

Publications and source records attributed to N Sanno.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expression of Ptx1 in the adult rat pituitary glands and pituitary cell lines: hormone-secreting cells and folliculo-stellate cells.

The pituitary homeobox1 gene (Ptx1) was initially identified as encoding a pituitary-restricted transcription factor for the proopiomelanocortin (POMC) gene. In order to elucidate the expression pattern of the Ptx1 protein, we investigated the localization of the protein in adult rat pituitary gland and in various pituitary cell lines. We produced an antibody specific for Ptxl protein, and confirmed its specificity by Western blot analysis. Immunohistochemically, many nuclei in the anterior pituitary cells as well as in the intermediate cells were positive for Ptxl staining with this specific antibody. Immunohistochemical double staining revealed the presence of Ptx1 not only in all types of hormone-secreting cells but also in some folliculo-stellate (FS) cells. Furthermore, the expression of Ptx1 mRNA was confirmed in various pituitary cell lines and in the FS cell line by using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Our studies indicated that Ptxl may not only play a role as a basic transcriptional factor for production of various hormones, but may also play some important role(s) in FS cells. Possible synergistic actions with other factors remain to be investigated. The novel finding of Ptx1 in FS cells is of particular interest, and may suggest that FS cells and hormone-secreting cells are derived from a common cellular ancestor.

Animals↗
PubMed1999

Distribution of adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide, and AM mRNA in the rat gastric mucosa by immunocytochemistry and in situ hybridization.

Adrenomedullin (AM) is a novel vasorelaxant peptide isolated from pheochromocytoma. Proadrenomedullin N-terminal 20 peptide (PAMP) is a hypotensive peptide generated by posttranslational enzymatic processing of a 185-amino acid pro-AM molecule, the same precursor as AM. In this study, we investigated localizations of these peptides by immunocytochemistry and AM mRNA by non-radioisotopic in situ hybridization followed by the streptavidin and biotin complex (ABC) method and catalyzed signal amplification (CSA) in the rat adrenal medulla and gastric mucosa. In the gastric mucosa, both AM- and PAMP-like immunoreactivities were found in the neuroendocrine cells, but PAMP-positive cells were more abundant than AM-positive ones. By immunoelectron microscopy, AM and PAMP were localized exclusively in the secretory granules. The distribution pattern of AM mRNA-positive cells, only a limited portion of which had AM and/or PAMP, was also similar to that of the two peptides. But AM mRNA was detected also in a few epithelial cells as well as neuroendocrine cells. The two peptides might play an important role in the control of local circulation in the rat stomach.

Adrenomedullin↗
PubMed1999

Pit-1 positive alpha-subunit positive nonfunctioning human pituitary adenomas: a dedifferentiated GH cell lineage?

Pit-1 is a transcription factor which has been reported to regulate differentiation toward GH, PRL and TSH in the anterior pituitary glands. In the human pituitary adenomas, Pit-1 is highly expressed in GH secreting and TSH secreting adenomas as it can well be anticipated. Interestingly, human non-functioning pituitary adenomas also express Pit-1, especially it was expressed in all alpha SU positive nonfunctioning adenomas. The human anterior pituitary cells are special in comparison with rodents in a finding that alpha SU is frequently colocalized with GH. As alpha SU is the first hormone appearing during fetal development in the rodent pituitary glands, it may be postulated that alpha SU Pit-1 positive cells undergo differentiation in the GH cell lineage. From this background, this paper proposes that "alpha SU positive Pit-1 Positive" cells are the ones in the GH cell lineage, more specifically a dedifferentiated cell lineage toward alpha SU/GH/Pit-1.

Adenoma↗
PubMed1999

Ectopic corticotroph adenoma in the cavernous sinus: case report.

OBJECTIVE AND IMPORTANCE: Adrenocorticotropin (ACTH)-secreting pituitary adenomas causing Cushing's disease are often difficult to identify because of their variable locations and their small size. This report presents histological evidence of an ectopic ACTH-secreting adenoma located entirely within the cavernous sinus. CLINICAL PRESENTATION: A 62-year-old woman presented with central obesity, hypertension, and osteoporosis. Endocrinological evaluation suggested the presence of an ACTH-secreting pituitary adenoma; however, imaging studies, including dynamic magnetic resonance imaging, did not reveal any visible lesions in the pituitary gland. Bilateral cavernous sinus sampling demonstrated a large central/peripheral ACTH gradient, with a right/left ACTH gradient. The patient was treated as having pituitary-dependent Cushing's disease, until she died suddenly as a result of acute respiratory failure. INTERVENTION: In a postmortem histological examination, an ACTH-secreting adenoma was found in the right cavernous sinus, which was completely surrounded by dura mater and had no direct connection with the pituitary gland. CONCLUSION: Although they are rare, such adenomas located in the cavernous sinus should be recognized as one of the reasons for inaccurate cavernous sinus sampling and the failure of transsphenoidal surgery for patients with ACTH-dependent Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed1999

Reduced growth hormone receptor messenger ribonucleic acid in an aged man with chronic malnutrition and growth hormone resistance.

A severely malnourished 87-yr-old man presented with hypoglycemia. Serum GH levels were elevated, and serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3, and GH-binding protein were extremely reduced. The patient's GH was biologically active. Administration of GH for 4 consecutive days resulted in a slight increment in serum IGF-I levels, but no elevation of serum IGF-binding protein-3. The expression of GH receptor messenger ribonucleic acid in the liver was greatly reduced. An autopsy revealed a Rathke's cleft cyst confined to the sella turcica. Immunohistochemical studies for GH showed that there was nothing to suggest a tumor overproducing GH. In addition, TSH levels were elevated in the presence of normal thyroid hormone levels, and there was a cluster of cells showing strong immunohistochemical staining for the TSH beta-subunit in the pituitary. In this patient, the decreased expression of GH receptor messenger ribonucleic acid in the liver may have been responsible for the GH resistance, which was probably caused by malnutrition.

Aged↗
PubMed1999

Pituitary somatotroph adenoma producing growth hormone (GH)-releasing hormone (GHRH) with an elevated plasma GHRH concentration: a model case for autocrine and paracrine regulation of GH secretion by GHRH.

An acromegalic patient with a pituitary somatotroph adenoma associated with an extremely elevated plasma GHRH concentration is presented. The preoperatively high concentration of plasma GHRH returned to the normal level after successful removal of the adenoma. GHRH production and GHRH gene expression were confirmed in the adenoma by studies including immunohistochemistry and in situ hybridization. Expression of GHRH receptor messenger ribonucleic acid was verified by in situ hybridization. Immunohistochemical double staining for GH and GHRH revealed their colocalization in single adenoma cells. These findings confirmed the autocrine or paracrine regulation of GH production by endogenous GHRH from the adenoma cells. GHRH synthesis in the pituitary gland has recently been demonstrated, however, there have been no previous reports of a GHRH-producing pituitary somatotroph adenoma associated with an elevated plasma GHRH concentration. The existence of this GHRH-producing adenoma suggests a possible role of locally generated GHRH in the progression of somatotroph adenomas, i.e. the monoclonally established somatotroph adenomas develop further under the influence of locally produced GHRH. The demonstration of GHRH production by this somatotroph adenoma is of importance in clarifying the autocrine or paracrine regulation of GH production and the progression of human somatotroph adenomas.

Acromegaly↗
PubMed1999

Expression of Rab3, a Ras-related GTP-binding protein, in human nontumorous pituitaries and pituitary adenomas.

Rab proteins are low molecular weight GTP-binding proteins. Among these proteins, the Rab3 isoforms are considered to be involved in the exocytosis of synaptic vesicles and secretory granules in the central nervous system and anterior pituitary gland. In recent reports, the expression of Rab3 isoforms in anterior pituitary glands of mammalian species was extensively investigated. In the present study, we investigated the localization of Rab3 protein in 5 human nontumorous pituitaries and 114 human pituitary adenomas using immunohistochemical methods. In five human nontumorous pituitaries, Rab3 protein was expressed in the cytoplasm of anterior pituitary cells. Double staining for anterior pituitary hormones revealed the expression of Rab3 in growth hormone-secreting cells, but rare expression was observed in the other anterior pituitary hormone-secreting cells. Among the pituitary adenomas, 71 (62.3%) of 114 pituitary adenomas were positive for Rab3. Among the different pituitary adenoma types, the incidence of Rab3 immunopositivity was highest in growth hormone-secreting adenomas (100%), followed by adrenocorticotropic hormone-secreting adenomas (71.4%), thyroid-stimulating hormone-secreting adenomas (57.1%), nonfunctioning adenomas (56.0%), and prolactin-secreting adenomas (33.3%). After an embedding immunoelectron microscopic study, Rab3 was localized along the limiting membrane of secretory granules in the Rab3-positive pituitary adenomas. Western blotting showed the molecular weight of Rab3 to be 25 kDa in the pituitary adenomas, which were immunohistochemically positive for Rab3 protein. These results suggested that Rab3 might be involved in regulating the exocytosis of secretory granules of the anterior pituitary cells, especially growth hormone-secreting ones, which are particularly characterized by densely granulated cytologic features.

Adenoma↗
PubMed1998

Expression of Pit-1 mRNA and activin/inhibin subunits in clinically nonfunctioning pituitary adenomas. In situ hybridization and immunohistochemical analysis.

The pituitary-specific transcriptional factor Pit-1 is known to play a role in the development and differentiation of pituitary cells. Recent investigations have suggested a role for this transcriptional factor in pituitary adenomas, especially growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas. In this study we analyzed the expression of Pit-1 mRNA and its protein in 24 clinically nonfunctioning pituitary adenomas in comparison with normal pituitary glands using in situ hybridization (ISH) and immunohistochemistry (IHC). The interaction between inhibin/activin, a member of the transforming growth factor-beta family, and Pit-1 was also studied. Immunohistochemically, Pit-1 protein was detected in 9 of 24 adenomas (37.5 %), and 8 of these 9 were also positive for the alpha subunit of glycoprotein (alphaSU). The expression of Pit-1 mRNA was detected in 14 of 24 (58.3%) clinically nonfunctioning adenomas, and it was found in all cases which expressed the Pit-1 protein. By the combined ISH and IHC method, Pit-1 mRNA was frequently observed in alphaSU-immunopositive cells in adenomas. The inhibin/activin alpha subunit was detected in all 24 adenomas and the betaA subunit was detected in 13 of 24 adenomas. The inhibin/activin betaA subunit was detected frequently with Pit-1 mRNA. From our observations, the inhibin/activin betaA subunit in nonfunctioning adenomas may have related the expression of Pit- mRNA in these adenomas.

Activins↗
PubMed1998

Cavernous sinus sampling in patients with adrenocorticotrophic hormone-dependent Cushing's syndrome with emphasis on inter- and intracavernous adrenocorticotrophic hormone gradients.

OBJECT: As an alternative method to inferior petrosal sinus sampling with administration of corticotropin-releasing hormone (CRH), the authors have developed a method of selective venous sampling directly from the cavernous sinus, which is performed using a superselective catheterization technique. The goal of this study is to assess this method. METHODS: Catheterization to the cavernous sinus was performed in 44 patients with clinical and biochemical features of Cushing's syndrome. Forty of these patients in whom there was a definite clinical and/or histological diagnosis were evaluated. In 35 patients, a pituitary microadenoma was detected on magnetic resonance imaging and/or during surgery. Ectopic lesions were suspected in five patients, who later developed nonpituitary tumors. The central/peripheral (C/P) ratios of adrenocorticotrophic hormone (ACTH) without CRH administration ranged from 5.2 to 448.1 (mean+/-standard deviation, 66.7+/-91.2) in cavernous sinuses and from 1.1 to 52 (mean+/-standard deviation, 8.5+/-9.9) in the inferior petrosal sinuses. The petrosal sinus sampling contained false negative results in eight patients (23%) based on a cutoff point of 2. On the contrary, patients with ectopic lesions did not show any increase in ACTH levels in either sampling portion. The intercavernous gradients of ACTH, ranging from 1.2 to 506.4, indicated the correct lateralization of microadenoma in the lateral wing in all 30 patients. The interpetrosal gradients, ranging from 1 to 31.4, did not give a sufficient value (> or = 1.4) in four patients (13%) with a lateral lesion. In five cases of midline tumors, the intercavernous and interpetrosal gradients indicated false laterality in three and four cases, respectively. The intracavernous (posterior-anterior) gradients, ranging from 1.04 to 60.7 (mean 14.9), showed a higher concentration of ACTH in the posterior portion of the sinus in all patients. CONCLUSIONS: These results suggest that 1) cavernous sinus sampling without CRH administration can demonstrate hypersecretion of ACTH from the pituitary gland with a high diagnostic accuracy; 2) intercavernous gradients will indicate the correct lateralization in laterally localized microadenomas; and 3) sampling should be performed from the posterior portion of the cavernous sinus.

Adolescent↗
PubMed1998

Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopy.

Prohormone convertase (PC) 1/3 and PC2 are involved in post-translational processing of endocrine tissues, including the pancreatic islets and pituitary glands. Our immunohistochemical studies disclosed the presence of PC1/3 and PC2 in non-neoplastic pituitary glands, especially in corticotrophs, gonadotrophs, and thyrotrophs. Among 58 pituitary adenomas obtained by trans-sphenoidal surgery, adrenocorticotropin (ACTH)-secreting adenomas showed a high incidence of the presence of PC1/3 and PC2, i.e., nine of nine cases were positive for ACTH. Five of nine cases showed consistency between PC2 localization and alpha-melanocyte stimulating hormone immunoreactivity, which suggests the functional correlation between PC2 and the processing of ACTH. In four cases, we observed inconsistency in immunolocalization, which suggested the possibility of inactive PC2 and abnormal processing of alpha-melanocyte stimulating hormone. The high incidence of PC1/3 and PC2 in nonfunctioning adenomas might be related to the processing of chromogranin A.

Adenoma↗
PubMed1997

Application of confocal laser scanning microscopy (CLSM) to visualize prolactin (PRL) and PRL mRNA in the normal and estrogen-treated rat pituitary glands using non-fluorescent probes.

In the present study, we performed concomitant visualization of immunohistochemistry (IHC) and in situ hybridization (ISH) on the materials processed for conventional light microscopic specimens using non-fluorescent Confocal Laser. Scanning Microscopy (CLSM). CLSM was used in the reflection confocal mode using horseradish peroxidase (HRP)-3-3'diaminobenzidine (DAB)-osmium (osmium black) and nitroblue tetrazolium (NBT) as non-fluorescent detection methods (probes). To obtain clearer images of the organelles, images that were built up as electronic signals in CLSM were processed in an image analysis system (IAS). By using the combination of CLSM and IAS, in IHC, immunohistochemical localization of prolactin (PRL) was in well-developed lamellar or whorling rough endoplasmic reticula (RER), Golgi apparatus, and secretory granules. With ISH, the expression and distribution of PRL messenger ribonucleic acid (mRNA) was observed in a fashion suggesting polysome-like structures on RER. These observations were confirmed by immunoelectron microscopy and electron microscopic ISH. The herein-described method is expected to be useful to perform the concomitant observation of IHC and ISH at subcellular levels using the conventional light microscopic specimens.

Animals↗