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Biomedical subjects

A Teramoto

Publications and source records attributed to A Teramoto.

At least 163 records · Page 9Linked to original sources

Mechanisms of action of somatostatin on human TSH-secreting adenoma cells.

The mechanisms of somatostatin (SRIH) action on thyroid-stimulating hormone (TSH) secretion were examined using human TSH-secreting adenoma cells. SRIH (10(-7) M) inhibited TSH secretion through a pertussis toxin-sensitive G protein. SRIH also inhibited forskolin- and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP)-induced TSH secretion. The mechanisms of this inhibition were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and by electrophysiological experiments. Application of 10(-7) M SRIH reduced the [Ca2+]i, whereas forskolin and 8-BrcAMP increased the [Ca2+]i. Simultaneous application of SRIH abolished the forskolin-and the 8-BrcAMP-induced [Ca2+]i increase, indicating that the SRIH-induced decrease in [Ca2+]i was independent of the reduction in intracellular cAMP. Under current clamp using the whole cell clamp, 10(-7) M SRIH hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials, which accounted for the SRIH-induced decrease in [Ca2+]i. Voltage clamp experiments revealed that this membrane hyperpolarization resulted from the activation of an inward-rectifying K+ current through a pertussis toxin-sensitive G protein. Intracellular injection of cAMP (100 microM) through the patch pipette did not abolish the SRIH-induced K+ current, indicating that the activation of SRIH-induced K+ channels was independent of intracellular cAMP. From these data, we concluded that SRIH-induced membrane hyperpolarization was responsible for the [Ca2+]i decrease, which in turn inhibited TSH secretion. Application of thyrotropin-releasing hormone (TRH; 10(-7) M) caused an increase in the [Ca2+]i, composed of an initial transient increase followed by a sustained increase. SRIH inhibited the sustained increase in [Ca2+]i. SRIH also inhibited the TRH-induced decrease in the membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

GH and PRL gene expression by nonradioisotopic in situ hybridization in TSH-secreting pituitary adenomas.

TSH-secreting pituitary adenomas are rare. The transcriptional expression (messenger ribonucleic acids: mRNAs) of TSH beta, GH, and PRL in five patients with TSH-secreting pituitary adenoma was studied by the in situ hybridization (ISH) method in order to elucidate their multiple hormone production. These patients showed inappropriately elevated serum TSH and alpha-subunit levels as well as pituitary mass lesions. The tissues from pituitary adenomas were obtained at the time of transsphenoidal surgery and revealed immunohistochemically the expression of alpha-subunit and TSH beta in all patients. Four adenomas were immunohistochemically associated with GH or PRL localization. The presence of pituitary-specific transcriptional factor Pit-1 was demonstrated in all adenomas in the nuclei of many cells. By ISH, signals for TSH beta mRNA were present in all five cases in many adenoma cells. Expression of GH mRNA and PRL mRNA were detected not only in four adenomas in which both hormonal products were immunolocalized but also in one adenoma that was immunohistochemically negative for GH and PRL. Combined staining by ISH and immunohistochemistry revealed the expression of GH mRNA and PRL mRNA in TSH beta-immunoreactive cells. Our findings indicate that TSH-secreting adenomas are multihormone-producing and could arise from precursor or stem cells rather than from differentiated TSH-secreting cells. It is suggested that ISH combined with immunohistochemistry may provide additional detailed information concerning the multidirectional histogenesis of this rare type of adenoma.

Adenoma↗

Acromegaly, diabetes insipidus, and visual loss caused by metastatic growth hormone-releasing hormone-producing malignant pancreatic endocrine tumor in the pituitary gland. Case report.

The case of a 52-year-old woman with acromegaly, diabetes insipidus, and visual impairment caused by a metastatic growth hormone-releasing hormone (GRH)-produced pancreatic tumor is reported. Serum growth hormone (GH) and somatomedin C levels were elevated to 14 ng/ml (normal < 5 ng/ml), and 3.20 U/ml (normal < 1.88 U/ml), respectively. Paradoxical increases were observed in GH levels after glucose tolerance and thyrotropin-releasing hormone-stimulation tests. Biopsy of a pituitary tumor observed on computerized tomography scans and magnetic resonance studies revealed a metastatic cancer. When circulating GRH levels were measured, a marked increase in plasma GRH (1145 pg/ml; normal < 4-1 pg/ml) was observed. The patient died of cachexia due to metastases. Postmortem examination revealed that a primary tumor, a malignant endocrine lesion, was present in the pancreas, with metastatic tumors in the pituitary, lung, liver, and adrenal glands. Synthesis and production of GRH by the tumor was demonstrated by Northern blotting and immunohistochemical analysis. The pituitary gland showed hyperplastic, but not adenomatous changes. The authors stress the importance of both exploration for an ectopic source of GRH and the search for a GH-producing pituitary adenoma when unusual signs and symptoms are seen in patients with acromegaly.

Acromegaly↗

Ultrastructural distribution of growth hormone and prolactin mRNAs in normal rat pituitary cells: a comparison between preembedding and postembedding methods.

In situ hybridization (ISH) at the electron microscopic level is essential for elucidating the intracellular distribution and role of mRNA in protein synthesis. We describe our electron microscopic ISH method using biotinylated oligonucleotide probes for rat growth hormone and prolactin mRNAs and compare the preembedding method with the postembedding method. Preembedding electron microscopic ISH localized rat growth hormone and prolactin mRNAs on the polysomes of the rough endoplasmic reticulum (RER). Rat growth hormone mRNA was distributed diffusely on the RER, whereas rat prolactin mRNA was scattered and distributed focally. Thus there might be a specific translational site for prolactin mRNA on the RER. Rat growth hormone mRNA signals were also recognized on the polysomes of the RER, using the postembedding method with streptavidin gold conjugate. The hybridization signal intensity using the postembedding method was lower, and non-specific signals were more frequent, in comparison with the preembedding method. The preembedding method thus appears to be easier and better than the postembedding method from the viewpoint of utility and preservation of mRNA. Electron microscopic ISH is considered to be an important tool for evaluating the intracellular localization of mRNA and the site of specific hormone synthesis on the RER.

Animals↗

Incidental pituitary lesions in 1,000 unselected autopsy specimens.

PURPOSE: To elucidate the frequency of false-positive results in imaging diagnoses of a functioning pituitary microadenoma, the authors studied various kinds of incidental lesions greater than 2 mm in diameter from a larger series of pituitary glands. MATERIALS AND METHODS: One thousand pituitary glands were studied in a nonselected autopsy series. Most causes of death were acute diseases or accidents. Each gland was fixed in 10% formalin and was then cut horizontally into three or four pieces, which were prepared for usual light microscopy. RESULTS: Of 178 glands found to have incidental lesions, 61 (34%) lesions were larger than 2 mm. Included were adenomas and hyperplasias (n = 20), Rathke cysts (n = 37), infarctions (n = 2), and hemorrhages (n = 2). Seventeen (74%) of 23 laterally localized lesions were adenomas, and 33 (87%) of 38 medially situated lesions were Rathke cleft cysts. These lesions were found in 5.8%-8.3% of subjects in every generation aged 30 years or older. CONCLUSION: Incidental lesions should be considered a cause of false-positive findings (6.1%) when an imaging diagnosis is made of a functioning pituitary microadenoma.

Adenoma↗

Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Suprasellar ectopic pituitary adenoma--case report.

A 33-year-old female presented with suprasellar ectopic pituitary adenoma manifesting as visual disturbances. Preoperative magnetic resonance imaging demonstrated intact pituitary gland and suprasellar cystic tumor, with a preoperative diagnosis of craniopharyngioma. At surgery, the tumor was identified as a suprasellar ectopic pituitary adenoma with intracapsular hematoma. There was no communication between the tumor and intrasellar structures. Total removal of the tumor immediately improved the severe visual disturbance. Ectopic pituitary adenoma should be considered in the differential diagnosis of a suprasellar lesion with intact pituitary gland.

Adenoma↗

Application of biotinylated oligonucleotide probes to the detection of pituitary hormone mRNA using northern blot analysis, in situ hybridization at the light- and electron-microscope levels.

There have been many reports on radioisotopic in situ hybridization (ISH) studies for the demonstration of pituitary hormone mRNAs in normal pituitary gland and pituitary adenomas. Recent studies have revealed that non-radioisotopic ISH has several advantages over the radioisotopic method. Using ISH with biotinylated oligonucleotide probes, we have been able to localize various pituitary hormone mRNAs in paraffin wax or frozen sections of rat normal pituitary gland and human pituitary adenomas. For control studies we used ISH with sense probes, ISH without probes, pretreatment with ribonuclease, ISH with a probe for beta-actin and Northern blot hybridization. Using biotinylated probes, gene transcripts of rat growth hormone and prolactin were detected by Northern blot hybridization. The same biotinylated probes were used not for light microscope ISH but also for the electron microscopical demonstration of rat growth hormone and prolactin mRNAs on the polysomes of the rough endoplasmic reticula. It is emphasized that biotinylated oligonucleotide probes are useful for the analysis of pituitary endocrine function because they are applicable to the three hybridization methods, namely, Northern blot hybridization and ISH at the light and electron microscope levels.

Adenoma↗

Clinical and immunohistochemical studies on TSH-secreting pituitary adenoma: its multihormonality and expression of Pit-1.

Eight patients with thyrotropin (TSH)-secreting pituitary adenoma are described. Serum TSH levels were inappropriately elevated in spite of elevated thyroid hormones. The serum-free glycoprotein alpha-subunit level was elevated in all the patients. The alpha-subunit to TSH molar ratio, a "tumor marker" for TSH-secreting adenoma, ranged from 1.06 to 6.16. All patients had macroadenoma and underwent transsphenoidal surgery. Light-microscopic indirect immunoperoxidase method applied on formalin-fixed paraffin-embedded specimens revealed alpha-subunit and TSH beta immunoreactivity in all adenomas. The proportion of TSH beta-positive cells ranged from 20% to 75% of adenoma cells. Six adenomas (75%) were associated with growth hormone (GH) and/or prolactine (PRL) immunoreactivity. By the double staining method, TSH beta and the alpha-subunit were frequently colocalized in the same cells, but some cells were found to contain either alpha-subunit or TSH beta. We also analyzed the localization of a pituitary-specific transcriptional factor, Pit-1, which has been suggested to play a role in functional differentiation toward growth hormone, prolactine, and TSH. All cases were positive for Pit-1 product using antibody against human Pit-1 synthesized peptide. Pit-1 product was localized in the nuclei of many adenoma cells and was frequently identified in cells that were positive for both TSH beta and growth hormone or prolactine. From our investigations, the role of Pit-1 in multidirectional differentiation during the development of TSH-secreting adenoma was suggested.

Adenoma↗

Selective venous sampling directly from cavernous sinus in Cushing's syndrome.

Using superselective catheterization technique, venous sampling directly from the cavernous sinus was performed in seven patients with Cushing's disease and one patient with ectopic ACTH secreting tumor. In Cushing's disease the central/peripheral (c/p) gradients of ACTH in the cavernous sinus (11.9-111.1; mean, 49.6) were much greater than those in the inferior petrosal sinus (1.0-52.0; mean, 14.0). The intercavernous gradients of ACTH provided correct lateralization in all patients but one who had a midline tumor. A patient with ectopic ACTH secreting tumor showed no gradients of ACTH both in the cavernous sinus and in the inferior petrosal sinus. The c/p gradients of PRL were smaller than those of ACTH in the cavernous sinus, inferior petrosal sinus, and jugular vein. The gradients of ACTH and PRL essentially indicated the same laterality in Cushing's disease, whereas the intersinus gradient of PRL provided a false laterality in two patients with a midline tumor. No complications have been observed during and after the sampling procedure. Thus, we conclude that 1) the selective sampling directly from the cavernous sinus offers sufficient c/p gradients (more than 10) for the reliable diagnosis of Cushing's disease, 2) CRH stimulation during the sampling and the simultaneous measurement of PRL are not necessary in this method, 3) the high concentration of pituitary hormones obtained by this sampling may be useful for other clinical investigations.

Adrenocorticotropic Hormone↗

Prepubescent pituitary null cell macroadenoma with silent macroscopic apoplexy: case report.

Secreting pituitary adenomas have marked prevalence in pediatric adenomas. We described a case of an 11-year-old boy with pituitary null cell macroadenoma with silent macroscopic pituitary apoplexy. The patient was admitted with bitemporal hemianopsia and a gradual deterioration of visual acuity. An endocrinological study revealed a low concentration of testosterone and in the plasma a decreased response of luteinizing hormone and follicle-stimulating hormone to luteinizing hormone-releasing hormone. This patient may be the first case of prepubescent null cell macroadenoma confirmed with immunohistochemical study in addition to the findings of classical histopathology.

Adenoma, Chromophobe↗

[Gonadotroph adenomas].

Gonadotroph adenomas have previously been considered to be a rare pituitary adenoma, because excessive secretion of gonadotropins does not always associate with its corresponding clinical syndrome. Therefore, these adenomas can be categorized as clinically non-functioning adenomas. However recent studies, including immunohistochemistry, electron microscopy, tissue culture, plaque assay, and in situ hybridization have classified gonadotroph adenomas may be more common than those it has been considered. In addition, many adenomas which previously have been categorized as non-functioning adenomas secrete gonadotropin and/or their subunits. In this paper, the clinicopathological characteristics of gonadotroph adenomas is reviewed.

Adenoma↗

[Clinical application of 11C-NMSP to the patients with pituitary adenoma other than prolactinoma].

The existence of dopamine D2 receptors in the pituitary adenoma is an important factor for bromocriptine therapy. In order to evaluate the D2 receptors in the pituitary adenoma, 11C-N-methylspiperone (NMSP) and positron emission tomography was performed in a variety of pituitary adenomas other than prolactinoma. Eight patients with pituitary adenoma including four non-functioning adenomas, two growth hormone (GH) secreting adenomas, one ACTH secreting adenoma and one TSH secreting adenoma and ten normal healthy volunteers were examined. 740 MBq of 11C-NMSP was injected and dynamic scan was performed from the time of injection to 80 min postinjection. The time dependent regional radioactivity in the striatum (st) and in the tumor tissue (tm) was measured and the binding rate, alpha, was calculated according to the following equation: Cst, tm/Ccbl = alpha x integral of t0 Ccbl dt/Ccbl + 1. The ratio of total radioactivity in the striatum or tumor over total activity in the cerebellum was plotted versus "normalized time", which was obtained by dividing integrated cerebellar radioactivity by actual cerebellar radioactivity for each timepoint. In three patients with pituitary adenoma, two scans were performed before and three hours after oral intake of 2.5 mg of bromocriptine. The alpha values for pituitary adenoma and normal striatum were 0.031 +/- 0.023 (0.017-0.088) and 0.042 +/- 0.006 (0.034-0.049), respectively. Bromocriptine reduced alpha value to various degree in pituitary adenoma (13-56%) but not in striatum (-3.7-3.3%). Our data suggests that in some of pituitary adenoma other than prolactinoma, dopamine D2 receptors existed but that nonspecific binding also contributed to the radioactivity in the tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Effects of activin A and somatostatin on intact FSH secretion and intracellular Ca2+ concentration in human FSH-secreting pituitary adenoma cells.

Activin A stimulated synthesis and secretion of intact FSH in dispersed human FSH-secreting adenoma cells. Significant stimulation was observed after 24 hr. Activin A caused an increase in Ca2+ concentration ([Ca2+]i). This response occurred soon after the activin A action. These effects were blocked in Ca(2+)-deficient medium and by nitrendipine (5 microM). Somatostatin inhibited the activin A-induced intact FSH secretion and the [Ca2+]i response. These findings indicated that Ca2+ influx through voltage-gated Ca2+ channel was involved in the activin A induced synthesis and secretion of intact FSH.

Activins↗