24 results on '"Shoichi Natori"'
Search Results
2. Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial
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Kohjiro Ueki, Takayoshi Sasako, Yukiko Okazaki, Masayuki Kato, Sumie Okahata, Hisayuki Katsuyama, Mikiko Haraguchi, Ai Morita, Ken Ohashi, Kazuo Hara, Atsushi Morise, Kazuo Izumi, Naoki Ishizuka, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki, Masakazu Haneda, Yasunori Iwashima, Toshihiro Suda, Naoki Tamasawa, Makoto Daimon, Jo Satoh, Noriko Takebe, Yasushi Ishigaki, Tsuyoshi Watanabe, Hiroaki Satoh, Kikuo Kasai, Yoshimasa Aso, Shun Ishibashi, Shigehiro Katayama, San-e Ishikawa, Masafumi Kakei, Kazuyuki Namai, Naotake Hashimoto, Yoshifumi Suzuki, Shunichiro Onishi, Koutaro Yokote, Masafumi Matsuda, Masahiro Masuzawa, Yoichi Hayashi, Satoshi Saito, Norikazu Ogihara, Hisamitsu Ishihara, Naoko Tajima, Kazunori Utsunomiya, Akira Shimada, Hiroshi Itoh, Ryuzo Kawamori, Hirotaka Watada, Michio Hayashi, Yasumichi Mori, Teruo Shiba, Akihiro Isogawa, Hiroshi Sakura, Masato Odawara, Kazuyuki Tobe, Kazuhisa Tsukamoto, Toshimasa Yamauchi, Tamio Teramoto, Yukio Hirata, Isao Uchimura, Yoshihiro Ogawa, Gen Yoshino, Takahisa Hirose, Hiroshi Kajio, Yoshihito Atsumi, Yoichi Oikawa, Atsushi Araki, Akio Ueki, Atsushi Ohno, Masafumi Kitaoka, Yoshikuni Fujita, Tatsumi Moriya, Taiki Tojo, Masayoshi Shichiri, Daisuke Suzuki, Masao Toyoda, Kumiko Hamano, Rieko Komi, Yasuo Terauchi, Nobuaki Kuzuya, Masayo Yamada, Toshinari Takamura, Mitsuo Imura, Hiroshi Tanaka, Masayuki Hayashi, Yasuhisa Kato, Mitsuyasu Itoh, Atsushi Suzuki, Mikihiro Nakayama, Takahisa Sano, Eitaro Nakashima, Yasuhiro Sumida, Yutaka Yano, Tsuyoshi Tanaka, Kazuya Murata, Atsunori Kashiwagi, Hiroshi Maegawa, Shigeo Kono, Nobuya Inagaki, Keisuke Kosugi, Tetsuyuki Yasuda, Yasunao Yoshimasa, Ichiro Kishimoto, Toshihiko Sato, Masayuki Hosoi, Tomoyuki Yamasaki, Munehide Matsuhisa, Iichiro Shimomura, Ataru Taniguchi, Akira Kuroe, Takeshi Kurose, Takeshi Ohara, Kazuhiko Sakaguchi, Mitsuyoshi Namba, Kohei Kaku, Masazumi Fujiwara, Ikki Shimizu, Keizo Ono, Osamu Ebisui, Yukio Tanizawa, Yosuke Okada, Shoichi Natori, Takehiko Kodera, Naoichi Sato, Makoto Ide, Kentaro Yamada, Fumio Umeda, Tomoaki Eto, Kazuo Mimura, Shinsuke Hiramatsu, Tomoaki Inoue, Ryoko Takei, Atsushi Ogo, Katsumi Eguchi, Eiji Kawasaki, Yuji Koide, Eiichi Araki, Hideaki Jinnouchi, Hiroaki Yamamoto, Mitsutaka Motoyoshi, Toru Hiyoshi, Yasushi Tanaka, Tadahisa Momoki, Koichiro Sato, Akihiko Yoneyama, Kenichi Ito, Hiroshi Sobajima, Hiroshi Ikegami, Masaki Ikeda, Hiroki Ikeda, Kenji Takahashi, Hirofumi Makino, Yasuo Ueda, and Masamitsu Nakazato
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,Coronary artery bypass surgery ,0302 clinical medicine ,Endocrinology ,Randomized controlled trial ,Japan ,law ,Internal medicine ,Diabetes mellitus ,Early Medical Intervention ,Internal Medicine ,Medicine ,Humans ,Myocardial infarction ,Mortality ,education ,Stroke ,Aged ,education.field_of_study ,business.industry ,Middle Aged ,medicine.disease ,Surgery ,Causality ,Blood pressure ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Female ,business ,Follow-Up Studies - Abstract
Summary Background Limited evidence suggests that multifactorial interventions for control of glucose, blood pressure, and lipids reduce macrovascular complications and mortality in patients with type 2 diabetes. However, safe and effective treatment targets for these risk factors have not been determined for such interventions. Methods In this multicentre, open-label, randomised, parallel-group trial, undertaken at 81 clinical sites in Japan, we randomly assigned (1:1) patients with type 2 diabetes aged 45–69 years with hypertension, dyslipidaemia, or both, and an HbA 1c of 6·9% (52·0 mmol/mol) or higher, to receive conventional therapy for glucose, blood pressure, and lipid control (targets: HbA 1c 1c 1c , and history of cardiovascular disease. Neither patients nor investigators were masked to group assignment. The primary outcome was occurrence of any of a composite of myocardial infarction, stroke, revascularisation (coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting), and all-cause mortality. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00300976. Findings Between June 16, 2006, and March 31, 2009, 2542 eligible patients were randomly assigned to intensive therapy or conventional therapy (1271 in each group) and followed up for a median of 8·5 years (IQR 7·3–9·0). Two patients in the intensive therapy group were found to be ineligible after randomisation and were excluded from the analyses. During the intervention period, mean HbA 1c , systolic blood pressure, diastolic blood pressure, and LDL cholesterol concentrations were significantly lower in the intensive therapy group than in the conventional therapy group (6·8% [51·0 mmol/mol] vs 7·2% [55·2 mmol/mol]; 123 mm Hg vs 129 mm Hg; 71 mm Hg vs 74 mm Hg; and 85 mg/dL vs 104 mg/dL, respectively; all p vs 283 [22%] in the conventional therapy group, p vs 129 [10%], p=0·0001), the frequencies of major adverse events did not differ between groups. Interpretation Our results do not fully support the efficacy of further intensified multifactorial intervention compared with current standard care for the prevention of a composite of coronary events, cerebrovascular events, and all-cause mortality. Nevertheless, our findings suggest a potential benefit of an intensified intervention for the prevention of cerebrovascular events in patients with type 2 diabetes. Funding Ministry of Health, Labour and Welfare of Japan, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Kissei Pharmaceutical, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Novo Nordisk, Ono Pharmaceutical, Pfizer, Sanwa Kagaku Kenkyusho, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda.
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- 2017
3. Chromogranin B (secretogranin I) promotes sorting to the regulated secretory pathway of processing intermediates derived from a peptide hormone precursor
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Shoichi Natori and Wieland B. Huttner
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beta-Lipotropin ,endocrine system ,Pro-Opiomelanocortin ,Neuropeptide ,Peptide hormone ,Cytoplasmic Granules ,Sulfur Radioisotopes ,Transfection ,Cell Line ,Mice ,Methionine ,Adrenocorticotropic Hormone ,Proopiomelanocortin ,Chromogranins ,Animals ,Cysteine ,Multidisciplinary ,biology ,Beta-Lipotropin ,Chromogranin A ,Biological Transport ,Recombinant Proteins ,Kinetics ,Biochemistry ,Cell culture ,biology.protein ,Protein Processing, Post-Translational ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Chromogranin B - Abstract
Chromogranin B (CgB, secretogranin I) is a widespread constituent of neuroendocrine secretory granules whose function is unknown. To determine whether CgB affects the sorting of peptide hormone and neuropeptide precursors to secretory granules, we overexpressed CgB in AtT-20 cells, which exhibit an only moderate capacity to sort proopiomelanocortin and proteolytic fragments derived therefrom. In mock-transfected AtT-20 cells, a substantial proportion of newly synthesized proopiomelanocortin and its two primary proteolytic products generated in the trans-Golgi network, the N-terminal 23-kDa fragment containing adrenocorticotropin and the C-terminal beta-lipotropin fragment, was secreted via the constitutive pathway. Two- to three-fold overexpression of CgB markedly reduced the constitutive secretion of the 23-kDa fragment, but not beta-lipotropin and tripled the amount of adrenocorticotropin generated and stored in secretory granules. Our results indicate the existence of neuroendocrine-specific helper proteins which promote the sorting from the trans-Golgi network to secretory granules of certain processing intermediates derived from peptide hormone and neuropeptide precursors and demonstrate that CgB functions as such.
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- 1996
4. Tumor-induced osteomalacia in a patient with a phosphaturic mesenchymal tumor revealing feature of an ossifying fasciitis of the left abdominal wall
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Shoichi Natori, Koichi Oba, Akira Takei, Yoshinao Oda, Ken Arai, and Kazuo Nakanishi
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Pathology ,medicine.medical_specialty ,Soft Tissue Neoplasm ,Hypophosphatemia ,Soft Tissue Neoplasms ,Phosphates ,Abdominal wall ,Mesenchymoma ,medicine ,Humans ,Fasciitis ,Abdominal Muscles ,Osteomalacia ,business.industry ,Ossification, Heterotopic ,General Medicine ,Middle Aged ,medicine.disease ,Phosphaturic mesenchymal tumor ,Fractures, Spontaneous ,medicine.anatomical_structure ,Feature (computer vision) ,Female ,business - Published
- 2002
5. Thyrotropin Releasing Hormone(TRH)-Induced Release of 7B2 (A Neuroendocrine Polypeptide) In Vivo and In Vitro Using Adenoma Cells of a Patient with Acromegaly
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Haruo Iguchi, Tetsuyuki Kitamoto, Hajime Nawata, Masao Ohashi, Michel Chrétien, and Shoichi Natori
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Adenoma ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Somatotropic cell ,Thyrotropin-releasing hormone ,Neuropeptide ,Nerve Tissue Proteins ,Neuroendocrine Secretory Protein 7B2 ,Basal (phylogenetics) ,Pituitary Gland, Anterior ,In vivo ,Thyrotropin-releasing hormone receptor ,Internal medicine ,Acromegaly ,Tumor Cells, Cultured ,medicine ,Humans ,Pituitary Neoplasms ,Thyrotropin-Releasing Hormone ,Chemistry ,General Medicine ,medicine.disease ,Pituitary Hormones ,Endocrinology ,Growth Hormone ,Secretory Rate ,hormones, hormone substitutes, and hormone antagonists - Abstract
We demonstrated TRH-induced release of 7B2 (a neuroendocrine polypeptide) in vivo and in vitro (somatotroph adenoma cells) in a patient with acromegaly. The mean basal plasma 7B2 and growth hormone (GH) levels before operation were 142.8 +/- 3.2 ng/l and 52.4 +/- 1.6 micrograms/l (mean +/- SEM), respectively and these levels significantly rose after an i.v. administration of 500 micrograms of thyrotropin releasing hormone (TRH). After the transsphenoidal adenomectomy, the basal level of plasma GH was restored to the normal level and that of plasma 7B2 was slightly decreased. In addition, TRH-induced response of plasma 7B2 and GH disappeared post-operatively. In a primary culture of somatotroph adenoma cells obtained at surgery, TRH significantly induced secretions of both 7B2 and GH. Immunohistochemical studies showed the positive 7B2 and GH immunoreactivities in somatotroph adenoma cells. These findings strongly suggest that the somatotroph adenoma cells in this case produced and released 7B2 concomitant with GH.
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- 1991
6. EFFECT OF OCTAPEPTIDE SOMATOSTATIN ANALOGUE (SMS 201-995) ON PLASMA 7B2 (A NEUROENDOCRINE POLYPEPTIDE) LEVELS IN PATIENTS WITH ACROMEGALY
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Haruo Iguchi, Hajime Nawata, Masao Ohashi, Shoichi Natori, Ryusuke Nakao, and Stephen R. Bloom
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Adenoma ,Adult ,Male ,medicine.medical_specialty ,Somatotropic cell ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Nerve Tissue Proteins ,Octreotide ,Neuroendocrine Secretory Protein 7B2 ,Subcutaneous injection ,Basal (phylogenetics) ,Endocrinology ,Pituitary adenoma ,Internal medicine ,Acromegaly ,Humans ,Medicine ,Pituitary Neoplasms ,Saline ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Pituitary Hormones ,Somatostatin ,Growth Hormone ,Female ,business - Abstract
We studied the sequential changes of plasma levels of immunoreactive '7B2' (IR-7B2), a neuroendocrine polypeptide, after a subcutaneous injection of 50 micrograms of synthetic octapeptide somatostatin analogue (SMS 201-995) in seven patients with acromegaly due to GH-producing pituitary adenoma. Compared to the basal levels, mean plasma IR-7B2 and GH levels significantly decreased, until 5 and 10 h respectively after the administration of SMS 201-995. The mean (+/- SEM) nadir levels of plasma IR-7B2 and GH were 68.1 +/- 10.1 and 13.1 +/- 6.9%, respectively, compared to mean plasma levels before treatment (100%). Plasma IR-7B2 as well as GH levels did not change significantly when saline was administered subcutaneously to three acromegalic patients. In addition, plasma IR-7B2 levels did not change significantly after the administration of SMS 201-995 in normal subjects or in patients with primary hypothyroidism in whom SMS 201-995 induced a decrease of plasma TSH levels. These results strongly suggest that SMS 201-995 has an unequivocal suppressive effect on the synthesis and/or the secretion of 7B2 in human somatotroph adenoma cells.
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- 1990
7. Chromogranin B (secretogranin I), a neuroendocrine-regulated secretory protein, is sorted to exocrine secretory granules in transgenic mice
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Shoichi Natori, Benio Tsuchiya, Andrea Hellwig, Haruo Iguchi, Ryoichi Takayanagi, Toru Kameya, Ursula Weiß, Angus King, Hajime Nawata, and Wieland B. Huttner
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Exocrine gland ,Secretory granule maturation ,Immunocytochemistry ,Golgi Apparatus ,Endocrine System ,Mice, Transgenic ,Cytoplasmic Granules ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Exocrine Glands ,medicine ,Chromogranins ,Animals ,Transgenes ,Molecular Biology ,Pancreas ,Enzyme Precursors ,General Immunology and Microbiology ,biology ,General Neuroscience ,Granule (cell biology) ,Chromogranin A ,Hydrogen-Ion Concentration ,Zymogen granule ,Immunohistochemistry ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Secretory protein ,Biochemistry ,Vacuoles ,biology.protein ,Research Article ,Chromogranin B - Abstract
Chromogranin B (CgB, secretogranin I) is a secretory granule matrix protein expressed in a wide variety of endocrine cells and neurons. Here we generated transgenic mice expressing CgB under the control of the human cytomegalovirus promoter. Northern and immunoblot analyses, in situ hybridization and immunocytochemistry revealed that the exocrine pancreas was the tissue with the highest level of ectopic CgB expression. Upon subcellular fractionation of the exocrine pancreas, the distribution of CgB in the various fractions was indistinguishable from that of amylase, an endogenous constituent of zymogen granules. Immunogold electron microscopy of pancreatic acinar cells showed co-localization of CgB with zymogens in Golgi cisternae, condensing vacuoles/immature granules and mature zymogen granules; the ratio of immunoreactivity of CgB to zymogens being highest in condensing vacuoles/immature granules. CgB isolated from zymogen granules of the pancreas of the transgenic mice aggregated in a mildly acidic (pH 5.5) milieu in vitro, suggesting that low pH-induced aggregation contributed to the observed concentration of CgB in condensing vacuoles. Our results show that a neuroendocrine-regulated secretory protein can be sorted to exocrine secretory granules in vivo, and imply that a key feature of CgB sorting in the trans-Golgi network of neuroendocrine cells, i.e. its aggregation-mediated concentration in the course of immature secretory granule formation, also occurs in exocrine cells although secretory protein sorting in these cells is thought to occur largely in the course of secretory granule maturation.
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- 1998
8. Regulated secretion. Helper proteins for neuroendocrine secretion
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Wieland B. Huttner and Shoichi Natori
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Proprotein convertase 2 ,Peptide ,Biology ,Cytoplasmic Granules ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Cytoplasmic granules ,Cell Line ,Enzyme activator ,Endopeptidases ,Regulated secretion ,Chromogranins ,Animals ,Secretion ,Subtilisins ,chemistry.chemical_classification ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Proteins ,Neurosecretory Systems ,Cell biology ,Enzyme Activation ,Proprotein Convertase 2 ,chemistry ,Cell culture ,General Agricultural and Biological Sciences ,Protein Processing, Post-Translational - Abstract
The granins, known to be general constituents of neuroendocrine secretory granules, are regulators of the proteolytic processing of peptide precursors and promote their aggregation-mediated sorting into secretory granules.
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- 1995
9. Acromegaly with hyperprolactinemia developed after bilateral adrenalectomy in a patient with Cushing's syndrome due to adrenocortical nodular hyperplasia
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Hajime Nawata, R. Yoshiyuki Osamura, Yasuhiro Kabayama, Masafumi Haji, Hiroshi Ibayashi, Takeshi Kanzaki, Atsushi Ogo, and Shoichi Natori
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Adenoma ,Adult ,endocrine system ,medicine.medical_specialty ,ACTH-Secreting Pituitary Adenoma ,Pathology ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Thyrotropin-releasing hormone ,Cushing syndrome ,Endocrinology ,Adrenocorticotropic Hormone ,Pituitary adenoma ,Internal medicine ,Acromegaly ,medicine ,Humans ,Pituitary Neoplasms ,Cushing Syndrome ,Hyperplasia ,business.industry ,Adrenalectomy ,Pituitary tumors ,medicine.disease ,Immunohistochemistry ,Hormones ,Prolactin ,Hyperprolactinemia ,Growth Hormone ,Adrenal Cortex ,Female ,business ,Tomography, X-Ray Computed ,hormones, hormone substitutes, and hormone antagonists - Abstract
A 27-yr-old woman was referred for evaluation of acromegaly and hyperprolactinemia. She had undergone left adrenalectomy at 12 and right adrenalectomy at 17 for Cushing's syndrome due to adrenocortical nodular hyperplasia. At this time a pituitary tumor was found by brain computerized tomography, but plasma levels of growth hormone (GH), prolactin (PRL) and adrenocorticotropin (ACTH) were normal. When she was 23, symptoms and signs of acromegaly and subsequently galactorrhea-amenorrhea had developed. Plasma GH and PRL were increased and she was followed up by the administration of bromocriptine (2.5 mg-12.5 mg/day, p.o.). However the plasma GH level had been increasing gradually. On admission, plasma GH and PRL were high (19.5 micrograms/L, 61.0 micrograms/L, respectively) and increased in response to thyrotropin releasing hormone (TRH, 500 micrograms i.v.). An intrasella mass, which had been detected when she was 17, had become enlarged and was removed by Hardy's operation. Microscopically, the resected tumor was an eosinophilic adenoma. Immunohistochemical studies showed GH, PRL and ACTH positive cells localized in the tumor. Immunoultrastructural analysis of the tumor confirmed that GH, PRL and ACTH were present in secretory granules and Golgi apparatus in the tumor cells. The patient was a rare case of acromegaly with hyperprolactinemia developed after bilateral adrenalectomy of Cushing's syndrome due to adrenocortical nodular hyperplasia, all of which manifestations may be caused by a GH, PRL and ACTH secreting pituitary adenoma.
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- 1993
10. Age-related change in 7B2 (a novel pituitary polypeptide) concentrations in human cerebrospinal fluid
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Stephen R. Bloom, Haruo Iguchi, Shoichi Natori, Shin-nosuke Kurose, and Hajime Nawata
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Male ,Aging ,medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Nerve Tissue Proteins ,Biochemistry ,Gel permeation chromatography ,Neuroendocrine Secretory Protein 7B2 ,Cellular and Molecular Neuroscience ,Endocrinology ,Cerebrospinal fluid ,Reference Values ,Age related ,Internal medicine ,Mole ,medicine ,Humans ,Chemistry ,Radioimmunoassay ,Pituitary Hormones ,Sephadex ,Reference values ,Female ,Quantitative analysis (chemistry) - Abstract
Concentrations of 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) were measured using a specific 7B2 radioimmunoassay (RIA) in cerebrospinal fluids (CSFs) from 87 humans. The mean (+/- S.E.M.) concentration of 7B2-IR in CSF was 2022 +/- 68 pM and a statistically significant decrease with aging was observed in those concentrations (R = -0.28, t = 2.73, P less than 0.01), although it was not a strong relation based on the R-value. In the gel permeation chromatography of CSF on Sephadex G-100, a major peak with an apparent mol. wt. of 43 kDa (43K) and a minor peak with that of 11 kDa (11K) were observed.
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- 1988
11. Age-related change in plasma concentration of 7B2 (a novel pituitary polypeptide) in normal humans
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Hajime Nawata, Shoichi Natori, Michel Chrétian, Ken-Ichi Kato, Hiroshi Ibayashi, and Haruo Iguchi
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Adult ,Liver Cirrhosis ,medicine.medical_specialty ,Pituitary gland ,Cirrhosis ,Radioimmunoassay ,Nerve Tissue Proteins ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Neuroendocrine Secretory Protein 7B2 ,Reference Values ,Internal medicine ,Age related ,medicine ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Aged ,Aged, 80 and over ,Kidney ,Age Factors ,General Medicine ,Middle Aged ,medicine.disease ,Molecular Weight ,Pituitary Hormones ,Specific radioimmunoassay ,medicine.anatomical_structure ,Endocrinology ,Plasma concentration ,Chromatography, Gel ,Kidney Failure, Chronic ,Female ,Endocrine gland - Abstract
Using a specific radioimmunoassay, we measured concentrations of plasma 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) in normal human subjects, patients with chronic renal failure and those with liver cirrhosis. Mean (+/- SEM) values of plasma 7B2-IR in normal healthy men and women were 55.8 +/- 1.2 pg/ml (n = 266) and 56.1 +/- 0.9 pg/ml (n = 408), respectively. The elevation of plasma 7B2-IR showed a relationship with age of the subjects, in both men (r = 0.39, t = 6.86, p less than 0.001) and women (r = 0.35, t = 7.44, p less than 0.001). Plasma 7B2-IR concentrations were elevated in patients with chronic renal failure (536 +/- 45 pg/ml, Mean +/- SEM, n = 10) as well as those in liver cirrhosis (95 +/- 10 pg/ml, Mean +/- SEM, n = 15) compared to values in normal subjects, suggesting that 7B2 is mainly eliminated through the kidney and is partly metabolized in the liver.
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- 1987
12. Growth Hormone Releasing Hormone-Sensitive Adenylate Cyclase Activity in Growth Hormone-Producing Pituitary Adenoma: Correlation to the Response of Plasma Growth Hormone to Growth Hormone Releasing Hormone in Patients with Acromegaly
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Shoichi Natori, Hajime Nawata, Masao Ohashi, Shoichiro Ikuyama, and Masafumi Haji
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Adenoma ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,Pituitary gland ,Radioimmunoassay ,Biology ,Growth Hormone-Releasing Hormone ,Endocrinology ,Pituitary adenoma ,Internal medicine ,Acromegaly ,Cyclic AMP ,medicine ,Humans ,Pituitary Neoplasms ,Insulin-Like Growth Factor I ,Cell Membrane ,General Engineering ,Middle Aged ,medicine.disease ,Growth hormone–releasing hormone ,Somatostatin ,medicine.anatomical_structure ,Growth Hormone ,Female ,Cyclase activity ,hormones, hormone substitutes, and hormone antagonists ,Intracellular ,Adenylyl Cyclases - Abstract
The correlation between response of plasma GH to GHRH and the GHRH-induced stimulation of the intracellular adenylate cyclase (AC) activity in pituitary adenoma cell membranes in acromegalic patients was investigated. Each peak plasma GH level after iv administration of GHRH ranged from 1.1 to 13.8 times the basal level in 13 acromegalic patients. On the other hand, the maximal stimulation of intracellular AC activity (cAMP production) induced by GHRH varied from 1.4 to 6.4 times the control level in each GH-producing pituitary adenoma cell membrane. A significant positive correlation (r = 0.89, P less than 0.005) between plasma GH response to GHRH and intracellular cAMP production stimulated by GHRH was observed in nine of the acromegalic patients. In contrast, the response of plasma GH to GHRH was significantly blunted, despite a fairly large production of intracellular cAMP stimulated by GHRH, in the other four acromegalic patients. These results suggest that GHRH-induced GH release from GH-producing pituitary adenomas of patients with acromegaly may be regulated not only by GHRH receptor-adenylate cyclase system but also modified by several other factors including somatostatin and Sm-C.
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- 1989
13. Presence of High Concentration of 7B2 in Pleural Effusion
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Haruo Iguchi, Kazuhiro Miyazaki, Mitsuo Ohta, Hajime Nawata, Shoichi Natori, Nobuyuki Hara, and Stephen R. Bloom
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Lung Diseases ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Pleural effusion ,Nerve Tissue Proteins ,Small-cell carcinoma ,Neuroendocrine Secretory Protein 7B2 ,Endocrinology ,Acromegaly ,medicine ,Carcinoma ,Humans ,Lung cancer ,Lung ,Chemistry ,General Engineering ,Radioimmunoassay ,respiratory system ,medicine.disease ,respiratory tract diseases ,Pleural Effusion ,Pituitary Hormones ,medicine.anatomical_structure ,Effusion ,Chromatography, Liquid - Abstract
7B2 (a novel pituitary protein) is a secretory protein in the neuroendocrine tissues and an increase in the plasma 7B2 concentration was noted in some patients with various endocrine tumors, including small cell carcinoma of the lung and acromegaly, suggesting that 7B2 is a possible marker for these tumors. Using a radioimmunoassay, the 7B2 concentration was measured in pleural fluid samples obtained from 36 patients with lung cancer and benign pulmonary disease to assess its concentration as a marker for small cell carcinoma of the lung (SCCL) or malignant effusion. 7B2-immunoreactivity (IR) was present in pleural fluid and its concentration was much higher than in plasma. However, there was no significant difference between pleural fluid 7B2 in patients with SCCL and in other histological types of lung carcinoma or in malignant and nonmalignant patients. In the chromatographic analysis of pleural fluid on gel permeation chromatography and reverse-phase high-performance liquid chromatography, there was no molecular heterogeneity between malignant and nonmalignant effusion. These results suggest that pleural fluid 7B2-IR is not a useful marker for SCCL or malignant effusion.
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- 1988
14. LHRH increases plasma 7B2 concentration in normal human subjects
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Masao Ohashi, Hajime Nawata, Haruo Iguchi, Shoichi Natori, and Michel Chrétien
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Adult ,Male ,endocrine system ,medicine.medical_specialty ,Time Factors ,Corticotropin-Releasing Hormone ,Nerve Tissue Proteins ,Gonadotropic cell ,Gonadotropin-Releasing Hormone ,Corticotropin-releasing hormone ,Basal (phylogenetics) ,Neuroendocrine Secretory Protein 7B2 ,Endocrinology ,Adrenocorticotropic Hormone ,Internal medicine ,medicine ,Humans ,business.industry ,General Engineering ,Luteinizing Hormone ,Pituitary Hormones ,Injections, Intravenous ,Female ,Follicle Stimulating Hormone ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
We studied the response of plasma 7B2 to LHRH and ovine corticotropin releasing hormone (o-CRH) in healthy young subjects. The plasma 7B2 concentration significantly increased from 78.3 +/- 7.5 (mean +/- SEM) to 102.0 +/- 6.0 ng/L (142.7 +/- 12.7% of the basal value; P less than 0.01) following iv administration of LHRH in seven young subjects. On the other hand, no increase in plasma 7B2 was found after iv administration of o-CRH in six young subjects. These results, together with our previous report of no increase in plasma 7B2 after administration of TRH and GHRH in young subjects, suggest that pituitary 7B2 may be present in gonadotrophs and be released only by LHRH in physiological conditions.
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- 1989
15. Phorbol ester and phospholipase C-induced growth hormone secretion from pituitary somatotroph adenoma cells in culture: effects of somatostatin, bromocriptine, and pertussis toxin
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Ken-Ichi Kato, Shoichiro Ikuyama, Hajime Nawata, Hiroshi Ibayashi, and Shoichi Natori
- Subjects
Adenoma ,Phosphatidylinositol 4,5-Diphosphate ,medicine.medical_specialty ,Somatotropic cell ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biology ,Pertussis toxin ,Phosphatidylinositols ,Biochemistry ,Endocrinology ,GTP-Binding Proteins ,Internal medicine ,Acromegaly ,medicine ,Humans ,Secretion ,Drug Interactions ,Pituitary Neoplasms ,Virulence Factors, Bordetella ,Bromocriptine ,Cells, Cultured ,Protein Kinase C ,Phospholipase C ,Biochemistry (medical) ,medicine.disease ,Growth hormone secretion ,Somatostatin ,Pertussis Toxin ,Growth Hormone ,Type C Phospholipases ,Tetradecanoylphorbol Acetate ,Secretory Rate ,medicine.drug - Abstract
To clarify the role of the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH secretion in human somatotrophs and the effects of inhibitors of GH secretion on this mechanism, we studied the effects of 12-tetradecanoylphorbol-13-acetate (TPA) and phospholipase C (Plase C) on GH secretion and the interactions of somatostatin (SRIH), bromocriptine, and pertussis toxin (IAP) with TPA or Plase C, using human GH-secreting pituitary adenoma cells in culture. SRIH (10(-9)-10(-7) M) inhibited and TPA (10(-10)-10(-8) M) and Plase C (0.125-1.0 U/mL) stimulated GH secretion. SRIH (10(-9)-10(-7) M) inhibited GH release induced by TPA (10(-8) M) or Plase C (1.0 U/mL). Bromocriptine (10(-8) M) also inhibited 10(-8) M TPA-induced GH secretion. When adenoma cells were treated with 100 ng/mL IAP for 24 h, basal and TPA-induced GH secretion rates did not change. However, the inhibitory effects of SRIH (10(-8) M) or bromocriptine (10(-8) M) on basal and 10(-8) M TPA-stimulated GH secretion were attenuated. In addition, IAP reduced GH secretion induced by 0.5 U/mL Plase C, while SRIH inhibition of Plase C-evoked GH release was diminished by IAP. We conclude that the hydrolysis of PIP2 by Plase C, which causes activation of protein kinase C by 1,2-diacylglycerol and Ca2+ mobilization by inositol 1,4,5-triphosphate, is a physiological intracellular mechanism leading to GH secretion in human somatotrophs; SRIH inhibits GH secretion mediated by this mechanism, and bromocriptine blocks at least protein kinase C-mediated GH release; the inhibitory guanine nucleotide-binding protein (Ni) is involved in these inhibitory effects of SRIH and bromocriptine; and Ni modulates the breakdown of PIP2 by Plase C.
- Published
- 1987
16. Elevation of plasma 7B2 (a novel pituitary protein) in cord blood at obstetrical delivery and the possible correlation with GH
- Author
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J.S.D. Chan, Hiroshi Ibayashi, Hajime Nawata, Haruo Iguchi, Ken-Ichi Kato, Shoichi Natori, Michel Chrétien, and Nabil G. Seidah
- Subjects
Male ,medicine.medical_specialty ,Placenta ,Radioimmunoassay ,Nerve Tissue Proteins ,Biology ,Umbilical cord ,General Biochemistry, Genetics and Molecular Biology ,Umbilical vein ,Gel permeation chromatography ,Neuroendocrine Secretory Protein 7B2 ,Pregnancy ,Internal medicine ,medicine.artery ,medicine ,Humans ,Insulin ,General Pharmacology, Toxicology and Pharmaceutics ,Insulin-Like Growth Factor I ,Fetus ,Infant, Newborn ,Umbilical artery ,General Medicine ,Anatomy ,Luteinizing Hormone ,Fetal Blood ,Molecular Weight ,Pituitary Hormones ,Endocrinology ,medicine.anatomical_structure ,Cord blood ,Growth Hormone ,Chromatography, Gel ,Electrophoresis, Polyacrylamide Gel ,Female ,Follicle Stimulating Hormone - Abstract
Plasma 7B2-immunoreactivity (7B2-IR) concentrations in umbilical artery (UA), umbilical vein (UV) and maternal vein (MV) were measured by RIA at the time of obstetrical delivery at term. Plasma 7B2-IR concentrations (Mean +/- SEM) in UA (N = 12), UV (N = 16) and MV (N = 16) were 725 +/- 69, 699 +/- 64 and 116 +/- 4.5 pg/ml, respectively. Plasma 7B2-IR concentrations in UA and UV were much higher than those in MV. There was no arterio-venous gradient between UA and UV. A trace amount of 7B2-IR (Mean +/- SEM, 226 +/- 16.8 pg/g tissue) was detected in the placental extracts. A statistically significant positive correlation (r = 0.7595, p less than 0.005) was found between plasma 7B2-IR and GH in the UV. Significant negative correlations between body weight of the neonates and plasma levels of GH (r = -0.6836, p less than 0.01) and 7B2-IR (r = -0.4939, p less than 0.05) were also apparent. When analyzing cord blood plasma using gel permeation chromatography and SDS-polyacrylamide gel electrophoresis, a major peak with an apparent molecular weight of 20,000 was observed. These findings suggest that 7B2-IR in UA and UV originates from the fetus and that 7B2-IR does not permeate through the placenta. The possibility of involvement of 7B2 in fetal growth warrants attention.
- Published
- 1987
17. Different processing of chromogranin B into GAWK-immunoreactive fragments in the bovine adrenal medulla and pituitary gland
- Author
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Haruo Iguchi, Ken-Ichi Kato, Shoichi Natori, Michel Chrétien, and Hajime Nawata
- Subjects
endocrine system ,Pituitary gland ,medicine.medical_specialty ,Nicotine ,endocrine system diseases ,Stimulation ,Nerve Tissue Proteins ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Anterior pituitary ,Pituitary Gland, Anterior ,Internal medicine ,medicine ,Chromogranins ,Animals ,Humans ,Chromaffin Granules ,Tissue Distribution ,General Pharmacology, Toxicology and Pharmaceutics ,neoplasms ,Peptide sequence ,Medulla ,Cells, Cultured ,Chromatography, High Pressure Liquid ,Antiserum ,Immunoassay ,Chromogranin A ,General Medicine ,digestive system diseases ,Peptide Fragments ,Molecular Weight ,medicine.anatomical_structure ,Endocrinology ,Adrenal Medulla ,biology.protein ,Chromatography, Gel ,Potassium ,Cattle ,Adrenal medulla ,Chromogranin B - Abstract
Summary Chromogranin B 420–493(GAWK)-like immunoreactivity (chromogranin B (420–493)-LI) was determined by radio-immunoassay using two different rabbit antisera, one raised against chromogranin B (420–436) (GAWK 1–17) (Ab420–436) and the other against chromogranin B 439–457 (GAWK 20–38) (Ab439–457), in bovine and human tissues. Chromogranin B (420–493)-LI was present in the bovine adrenal medulla chromaffin granules as well as in the anterior pituitary gland and was released from the cultured bovine chromaffin cells by stimulation with high K + or nicotine. Chromogranin B (420–493)-LI present in the bovine tissues was detected using Ab420–436 but was not detected using Ab439–457. In the human tissues, chromogranin B (420–493)-LI was detected using Ab420–436 as well as Ab439–457. This suggests that the amino acid sequence of this region (chromogranin B 439–457) is different between human and bovine. On the gel permeation chromatography, chromogranin B (420–493)-LI was eluted at the void volume in the bovine adrenal medulla and at an apparent molecular weight of 4000 in the anterior pituitary gland. On the reverse-phase high-performance liquid chromatography, multiple peaks of chromogranin B (420–493)-LI was detected in the bovine adrenal medulla while one component of chromogranin B (420–493)-LI was found in the anterior pituitary gland. These results suggest that chromogranin B is processed into small fragments of chromogranin B (420–493)-LIs and that this processing is tissue-specific.
- Published
- 1988
18. Remarkable changes in the plasma levels of pituitary protein '7B2' during childhood
- Author
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Shoichi Natori, Ken-Ichi Kato, Hajime Nawata, Naoki Takayanagi, Haruo Iguchi, Hitoshi Kohno, and Yuichi Niida
- Subjects
Adult ,Male ,medicine.medical_specialty ,Aging ,Adolescent ,Nerve Tissue Proteins ,Gonadotropin-Releasing Hormone ,chemistry.chemical_compound ,Neuroendocrine Secretory Protein 7B2 ,Dehydroepiandrosterone sulfate ,Internal medicine ,medicine ,Humans ,Child ,Infusions, Intravenous ,Aged ,Aged, 80 and over ,business.industry ,Infant, Newborn ,Infant ,Plasma levels ,Middle Aged ,Pituitary Hormones ,Endocrinology ,chemistry ,Child, Preschool ,Pituitary Gland ,Pediatrics, Perinatology and Child Health ,Chromatography, Gel ,Female ,business ,Luteinizing hormone ,Adult level ,Hormone - Abstract
We measured plasma immunoreactive (IR)-7B2 concentrations in 96 children (57 males and 39 females) from the newborn period to 20 yr of age. Plasma IR-7B2 concentrations in infants less than 2 yr of age (range 175-580 pg/ml, n = 19) were much higher than those in adults (range 20-138 pg/ml). Plasma levels of IR-7B2 decreased with age during childhood to reach the adult level at 15-20 yr. Significant negative correlations were found between plasma levels of IR-7B2 and dehydroepiandrosterone sulfate (r = -0.4154, p less than 0.05, n = 27), luteinizing hormone (r = -0.4948, p less than 0.05, n = 20) and follicle-stimulating hormone (r = -0.4682, p less than 0.05, n = 20). The possibility of a relationship between the reduction of plasma IR-7B2 levels and pubertal development warrants attention.
- Published
- 1988
19. Presence of the novel pituitary protein '7B2' in bovine chromaffin granules: possible co-release of 7B2 and catecholamine as induced by nicotine
- Author
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H. Iguchi, Nabil G. Seidah, Michel Chrétien, Ken-Ichi Kato, Hiroshi Ibayashi, John S.D. Chan, Shoichi Natori, and Hajime Nawata
- Subjects
endocrine system ,medicine.medical_specialty ,Nicotine ,Nerve Tissue Proteins ,Cell Fractionation ,Biochemistry ,Cellular and Molecular Neuroscience ,Neuroendocrine Secretory Protein 7B2 ,Catecholamines ,Anterior pituitary ,Pituitary Gland, Anterior ,Internal medicine ,medicine ,Animals ,Chromaffin Granules ,Medulla ,Cells, Cultured ,Gel electrophoresis ,Chemistry ,Molecular Weight ,Pituitary Hormones ,medicine.anatomical_structure ,Secretory protein ,Endocrinology ,Cell culture ,Adrenal Medulla ,Chromaffin cell ,Chromaffin System ,Catecholamine ,Chromatography, Gel ,Potassium ,Cattle ,Adrenal medulla ,medicine.drug - Abstract
We observed the presence of the novel pituitary protein "7B2" and its release in the bovine adrenal medulla. The 7B2 concentration (mean +/- SEM) in extracts of the bovine adrenal medulla was 952 +/- 155 pg/mg tissue (n = 6). 7B2 was distributed in the chromaffin granule fraction prepared from the bovine adrenal medulla and was released by high K+ and/or nicotine from cultured cells of the bovine adrenal medulla. Co-release of 7B2 with catecholamine induced by nicotine from the cultured bovine chromaffin cells was also observed. In an analysis of the bovine adrenal medulla chromaffin granule fraction on gel permeation chromatography, there was a major peak with an apparent molecular weight of 45,000, whereas a major peak with an apparent molecular weight of 20,000 was found in that on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On reverse-phase HPLC, a major peak with a retention time of 35 min was observed in the bovine chromaffin granule fraction and in the bovine anterior pituitary extract. These findings indicate that 7B2 is a secretory protein in the bovine adrenal medulla. The possibility that 7B2 might be released with catecholamine, possibly in response to stress, warrants investigation.
- Published
- 1987
20. Characterization of growth hormone-releasing hormone receptors in pituitary adenomas from patients with acromegaly
- Author
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Hajime Nawata, Wylie Vale, Ken-Ichi Kato, Shoichiro Ikuyama, Shoichi Natori, Jean Rivier, Toshitsugu Kariya, Takahiro Sakai, and Hiroshi Ibayashi
- Subjects
Adenoma ,Adult ,Male ,endocrine system ,Pituitary gland ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Vasoactive intestinal peptide ,Receptors, Cell Surface ,Growth Hormone-Releasing Hormone ,Biochemistry ,Endocrinology ,Internal medicine ,Acromegaly ,medicine ,Humans ,Pituitary Neoplasms ,Receptor ,Chemistry ,Biochemistry (medical) ,Cell Membrane ,Middle Aged ,Ligand (biochemistry) ,Growth hormone–releasing hormone ,medicine.disease ,Dissociation constant ,medicine.anatomical_structure ,Growth Hormone ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
GHRH receptors in pituitary adenoma cell membranes from five patients with acromegaly were characterized using [125I] [His1,Nle27]GHRH-(1-32)NH2 ([125I]GHRHa) as a ligand. Specific binding of [125I]GHRHa to adenoma cell membranes was maximal within 20 min at 24 C, remained stable for 60 min, and was reversible in the presence of 500 nmol/L human GHRH-(1-44)NH2 (hGHRH). The specific binding increased linearly with 10-160 micrograms cell membrane protein. This binding was inhibited by 10(-11)-10(-6) mol/L hGHRH in a dose-dependent manner, with an ID50 of 0.20 nmol/L, but not by 10(-7) mol/L vasoactive intestinal peptide, glucagon, somatostatin-14, somatostatin-28, TRH, LHRH, and CRH. The specific binding of [125I]GHRHa to the membranes was saturable, and Scatchard analysis of the data revealed an apparent single class of high affinity GHRH receptors in five adenomas from acromegalic patients; the mean dissociation constant was 0.30 +/- 0.07 (+/- SE) nmol/L, and the mean maximal binding capacity was 26.7 +/- 7.0 (+/- SE) fmol/mg protein. In three nonfunctioning pituitary adenomas, GHRH receptors were not detected. The plasma GH response to hGHRH (100 micrograms) injection was studied in four acromegalic patients before surgery. Plasma GH levels increased variably in response to hGHRH injection in all four patients. However, there was no correlation between the characteristics of the tumor GHRH receptors and plasma GH responsiveness in these patients. We conclude that pituitary GH-secreting adenomas have specific GHRH receptors. Exogenously administered GHRH presumably acts via these receptors, but the variations in plasma GH responsiveness to hGHRH in these patients cannot be directly related to the variations in binding characteristics of the GHRH receptors on the GH-secreting adenoma cells.
- Published
- 1988
21. Plasma 7B2 (a novel pituitary protein) immunoreactivity concentrations in patients with various endocrine disorders
- Author
-
Masao Ohashi, Shoichi Natori, Haruo Iguchi, and Hajime Nawata
- Subjects
Adult ,Male ,Pituitary gland ,medicine.medical_specialty ,Adolescent ,Nerve Tissue Proteins ,Endocrine System Diseases ,Hyperthyroidism ,Hypopituitarism ,Pheochromocytoma ,Basal (phylogenetics) ,Neuroendocrine Secretory Protein 7B2 ,Endocrinology ,Adrenocorticotropic Hormone ,Hypothyroidism ,Internal medicine ,Acromegaly ,medicine ,Endocrine system ,Humans ,Prolactinoma ,Cushing Syndrome ,Aged ,business.industry ,Thyroid ,General Engineering ,Middle Aged ,medicine.disease ,Pituitary Hormones ,medicine.anatomical_structure ,Medullary carcinoma ,Female ,business - Abstract
We have measured plasma 7B2 (a novel pituitary protein)-immunoreactivity (IR) concentrations in patients with various endocrine disorders. Mean (+/- SEM) basal plasma 7B2-IR concentrations (ng/L) in patients with acromegaly (81 +/- 14.6), Cushing's disease (57.2 +/- 8.5), prolactinoma (71.4 +/- 9.5), panhypopituitarism (50.6 +/- 7.6), isolated ACTH deficiency (47.9 +/- 11.6), hyperthyroidism (57.9 +/- 6.7) and hypothyroidism (60.8 +/- 9.4) were on the same levels as those in age-matched normal subjects. However, basal plasma 7B2-IR concentrations were increased to more than 100 ng/L in 5 out of 25 patients with acromegaly (20%). Mean basal plasma 7B2-IR concentrations in patients with medullary carcinoma of the thyroid and pheochromocytoma were 293 +/- 38.1 ng/L (range: 225.7-357.4 ng/L, n = 3) and 221 +/- 82.8 ng/L (range: 48.5-527.8 ng/L, n = 5), respectively, and significantly higher than those in age-matched normal subjects (P less than 0.001). These results suggest that plasma 7B2-IR may have some diagnostic value for acromegaly and may be useful as a marker for medullary carcinoma of the thyroid and pheochromocytoma.
- Published
- 1988
22. Evidence for the release of a novel pituitary polypeptide (7B2) from the growth hormone-producing pituitary adenoma of patients with acromegaly
- Author
-
Ken-Ichi Kato, Shoichi Natori, Haruo Iguchi, Hiroshi Ibayashi, Hajime Nawata, Hiroyuki Nakagaki, and Michel Chrétien
- Subjects
Adenoma ,Adult ,Male ,endocrine system ,Pituitary gland ,medicine.medical_specialty ,Somatotropic cell ,Corticotropin-Releasing Hormone ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Nerve Tissue Proteins ,Biochemistry ,Gonadotropin-Releasing Hormone ,Basal (phylogenetics) ,Cushing syndrome ,Neuroendocrine Secretory Protein 7B2 ,Endocrinology ,Oral administration ,Internal medicine ,Acromegaly ,Tumor Cells, Cultured ,Medicine ,Humans ,Pituitary Neoplasms ,Thyrotropin-Releasing Hormone ,Prolactinoma ,Bromocriptine ,business.industry ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,Pituitary Hormones ,medicine.anatomical_structure ,Growth Hormone ,Potassium ,Female ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
We studied the release of the pituitary polypeptide 7B2 in normal subjects and patients with acromegaly. Plasma 7B2 concentrations did not increase in response to human GHRH and TRH in normal subjects. Plasma 7B2 concentrations significantly increased from 124.4 +/- 39.9 (mean +/- SE) to 206.9 +/- 55.9 ng/L (180.8 +/- 17.9% of the basal value; P less than 0.01) 15 min after iv administration of GHRH in eight acromegalic patients, but they did not increase in nine other acromegalic patients. Mean plasma 7B2 levels increased from 68.8 +/- 17.9 to 168.7 +/- 53.5 ng/L (241.8 +/- 34.2% of the basal value; P less than 0.005) 30 min after iv administration of TRH in four acromegalic patients, but the two other patients tested had no response. No elevations of plasma 7B2 were found after iv administration of ovine CRH in six patients with Cushing's disease and after iv administration of TRH and/or oral administration of bromocriptine in six prolactinoma patients. In experiments using cultured human somatotroph adenoma cells, high K+ induced 7B2 release. The apparent mol wt of 7B2 in plasma was 20,000, whereas that of 7B2 in the culture medium was about 45,000. These findings suggest that 7B2 is secreted by human GH-producing pituitary adenoma cells and that plasma 7B2 responses to GHRH and/or TRH may be characteristics of human somatotroph adenomas.
- Published
- 1988
23. Plasma levels of 7B2 (a novel pituitary polypeptide) and its molecular forms in plasma and urine in patients with chronic renal failure: possible degradation by the kidney
- Author
-
Ken-Ichi Kato, Hajime Nawata, Hiroshi Ibayashi, Shoichi Natori, Haruo Iguchi, Stephen R. Bloom, and Yukinori Ou
- Subjects
Adult ,Male ,Pituitary gland ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Radioimmunoassay ,Renal function ,Nerve Tissue Proteins ,Urine ,Kidney ,Kidney Function Tests ,Biochemistry ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Neuroendocrine Secretory Protein 7B2 ,Endocrinology ,Internal medicine ,medicine ,Humans ,Blood urea nitrogen ,Aged ,Aged, 80 and over ,Creatinine ,Beta-2 microglobulin ,Chemistry ,Middle Aged ,Pituitary Hormones ,medicine.anatomical_structure ,Chromatography, Gel ,Kidney Failure, Chronic ,Electrophoresis, Polyacrylamide Gel ,Female ,Hemodialysis - Abstract
Plasma immunoreactive (IR)-7B2 was measured in patients with chronic renal failure (CRF), using a specific radioimmunoassay. The mean (± S.E.M.) concentration of plasma IR-7B2 in CRF patients under hemodialysis (502 ± 36 pg/ml, n = 27) was significantly higher than that in normal subjects (men, 52.9 ± 1.7 pg/ml ( n = 179); women, 55.8 ± 1.3 pg/ml ( n = 198)). Significant correlations between plasma levels of IR-7B2 and those of blood urea nitrogen, creatinine and β 2 -microglobulin were evident in non-dialyzed CRF patients. In the analyses of pooled plasma and urine obtained from normal subjects on gel permeation chromatography, a major peak of IR-7B2 was observed at an apparent molecular weight of 20,000 in the plasma, and at a position of a smaller molecular weight in the urine. These results suggest that 7B2 is degraded mainly in the kidney and that measurement of plasma 7B2 may serve as an appropriate tool for assessing renal function.
- Published
- 1988
24. Effect of GRF and somatostatin on 7B2 secretion by rat GH1 cells
- Author
-
Haruo Iguchi, Hajime Nawata, and Shoichi Natori
- Subjects
Adenoma ,endocrine system ,Pituitary gland ,medicine.medical_specialty ,Nerve Tissue Proteins ,Pituitary neoplasm ,Biology ,Growth Hormone-Releasing Hormone ,Octreotide ,Neuroendocrine Secretory Protein 7B2 ,Endocrinology ,Internal medicine ,medicine ,Tumor Cells, Cultured ,Somatostatin receptor 2 ,Animals ,Secretion ,Pituitary Neoplasms ,Delta cell ,General Engineering ,Growth hormone–releasing hormone ,Rats ,Pituitary Hormones ,Secretory protein ,Somatostatin ,medicine.anatomical_structure ,Growth Hormone ,Chromatography, Gel ,Potassium ,hormones, hormone substitutes, and hormone antagonists - Abstract
A novel pituitary protein "7B2" was secreted by GH1 cells. The secretion of 7B2 was increased in the presence of human GRF in a dose-responsive manner. In contrast, a somatostatin analog, SMS 201-995, revealed the inhibitory effects on the basal- and GRF-induced secretion of 7B2 at the concentration of 10(-7) M. These findings suggest that 7B2 is a secretory protein of rat GH1 cells under certain conditions.
- Published
- 1989
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