Search Results
You are looking at 1 - 10 of 10 items for
- Author: Y. Nakai x
- Refine by access: All content x
Search for other papers by J. Fukata in
Google Scholar
PubMed
Search for other papers by T. Usui in
Google Scholar
PubMed
Search for other papers by Y. Naitoh in
Google Scholar
PubMed
Search for other papers by Y. Nakai in
Google Scholar
PubMed
Search for other papers by H. Imura in
Google Scholar
PubMed
ABSTRACT
The effects of recombinant human interleukin (rhIL)-1α, -1β, 2 and 6 on the release of ACTH from the ACTH-producing tumour cell line AtT-20 of the mouse were studied during relatively long periods of incubation. Levels of ACTH in the media, measured by radioimmunoassay, were increased by the addition of rhIL-1α or -1β after latent periods of more than 4 h. RhIL-1α and -1β were almost equally potent in this experiment and the minimum, half-maximum and maximum effective concentrations of both rhIL-1α and -1β were about 0·1 pmol/l, 1–3 pmol/l and 10–100 pmol/l respectively. During incubation with rhIL-1β, immunoreactive ACTH levels and mRNA levels of the ACTH precursor pro-opiomelanocortin in cells also increased without apparent changes in the growth rate of the cells. Although the AtT-20 cells used in this study were quite insensitive to human/rat corticotrophin-releasing hormone (CRH), the cells showed a significant response to CRH after incubation with rhIL-1β. RhIL-6 showed similar effects to those of rhIL-1β on ACTH synthesis and release; increasing ACTH in cells and media after a certain latent period. On the other hand, rhIL-2 did not change ACTH levels in the AtT-20 cells in this study. These observations indicate that rhIL-1α, -1β and rhIL-6 have direct effects on ACTH-producing cells to stimulate the release and synthesis of ACTH after a latent period.
Journal of Endocrinology (1989) 122, 33–39
Search for other papers by T. Tominaga in
Google Scholar
PubMed
Search for other papers by J. Fukata in
Google Scholar
PubMed
Search for other papers by Y. Naito in
Google Scholar
PubMed
Search for other papers by Y. Nakai in
Google Scholar
PubMed
Search for other papers by S. Funakoshi in
Google Scholar
PubMed
Search for other papers by N. Fujii in
Google Scholar
PubMed
Search for other papers by H. Imura in
Google Scholar
PubMed
ABSTRACT
We have examined the mechanism by which corticostatin-I (CS-I) acts to attenuate ACTH-induced steroidogenesis in rat adrenal cells. CS-I inhibited ACTH-induced corticosterone production in a dosedependent manner, without any effects on the basal corticosterone level in adrenal cells. When the cells were stimulated by 100 pg ACTH/ml, the minimum effective concentration of CS-I was 100 ng/ml, and 0.3–1.0 μg CS-I/ml produced a 50% reduction of the stimulated corticosterone production. The inhibitory effect of CS-I on ACTH-stimulated corticosterone production became apparent within 15 min of incubation, and the effect was reversed quickly by the removal of CS-I from the media. CS-I had no effect on angiotensin II-stimulated aldosterone production by adrenal zona glomerulosa cells. CS-I also did not affect cyclic AMP- or forskolin-stimulated corticosterone production. In an in-vitro binding study using 125I-labelled CS-I, CS-I showed considerable specific binding to rat adrenal cells, and the binding competed with ACTH in a dose-dependent manner. These experiments suggest that CS-I competes with ACTH on their binding sites and exerts an inhibitory effect on the adrenal cells.
Journal of Endocrinology (1990) 125, 287–292
Search for other papers by T Mano in
Google Scholar
PubMed
Search for other papers by R Sinohara in
Google Scholar
PubMed
Search for other papers by Y Sawai in
Google Scholar
PubMed
Search for other papers by N Oda in
Google Scholar
PubMed
Search for other papers by Y Nishida in
Google Scholar
PubMed
Search for other papers by T Mokuno in
Google Scholar
PubMed
Search for other papers by K Asano in
Google Scholar
PubMed
Search for other papers by Y Ito in
Google Scholar
PubMed
Search for other papers by M Kotake in
Google Scholar
PubMed
Search for other papers by M Hamada in
Google Scholar
PubMed
Search for other papers by A Nakai in
Google Scholar
PubMed
Search for other papers by A Nagasaka in
Google Scholar
PubMed
Abstract
To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1·5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals.
These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism.
Journal of Endocrinology (1995) 147, 361–365
Search for other papers by N Nakao in
Google Scholar
PubMed
Search for other papers by Y Higashimoto in
Google Scholar
PubMed
Search for other papers by T Ohkubo in
Google Scholar
PubMed
Search for other papers by H Yoshizato in
Google Scholar
PubMed
Search for other papers by N Nakai in
Google Scholar
PubMed
Search for other papers by K Nakashima in
Google Scholar
PubMed
Search for other papers by M Tanaka in
Google Scholar
PubMed
Growth hormone receptor (GHR) cDNA and gene of the Japanese flounder (Paralicthys olivaceus) were cloned and their molecular structures were characterized. The 641 amino acid sequence predicted from the cDNA sequence showed more than 75% overall sequence similarity with GHRs of other teleosts such as turbot and goldfish, and contained common structural features of vertebrate GHRs. The extracellular domain of flounder GHR had three pairs of cysteines and an FGEFS motif with a replacement E to D. The cytoplasmic domain contained two conserved motifs referred to as box 1 and box 2. The flounder GHR gene was cloned by PCR using primers designed from the sequence of the GHR cDNA. The GHR gene was composed of 10 exons. The sequence of exon 1 corresponded to the 5'-untranslated region of the cDNA, and exons 2-6 encoded most parts of the extracellular domain. The transmembrane domain was found in exon 7, and the intracellular domain was encoded in exons 8-10. Exon 10 also encoded the 3'-untranslated region. Comparison of the flounder GHR gene with the human GHR gene shows that the flounder gene contains no exons corresponding to exon 3 of the human GHR gene, and that the region corresponding to exon 10 in the human GHR gene is encoded by exons 9 and 10 in the flounder GHR gene. These findings indicate that the flounder GHR gene diverged from those of mammalian and avian GHR genes, especially in the organization of the exons encoding the cytoplasmic domain. In addition to the regular form of GHR mRNA, a 3'-truncated form lacking the region derived from exons 9 and 10 was detected as a minor species in the liver by RT-PCR and by RNase protection assay. RT-PCR analysis showed that both the regular and the 3'-truncated GHR mRNAs are expressed in a wide range of flounder tissues with the highest levels being found in the liver. The 5'-flanking region of the flounder GHR gene was cloned by inverse PCR, and three transcription start points were identified with similar frequency by RNase protection assay.
Search for other papers by T Mano in
Google Scholar
PubMed
Search for other papers by R Sinohara in
Google Scholar
PubMed
Search for other papers by Y Sawai in
Google Scholar
PubMed
Search for other papers by N Oda in
Google Scholar
PubMed
Search for other papers by Y Nishida in
Google Scholar
PubMed
Search for other papers by T Mokuno in
Google Scholar
PubMed
Search for other papers by M Kotake in
Google Scholar
PubMed
Search for other papers by M Hamada in
Google Scholar
PubMed
Search for other papers by R Masunaga in
Google Scholar
PubMed
Search for other papers by A Nakai in
Google Scholar
PubMed
Search for other papers by A Nagasaka in
Google Scholar
PubMed
Abstract
Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state.
Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured.
A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2 −.
These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat.
Journal of Endocrinology (1995) 145, 131–136
Search for other papers by Y Itoh in
Google Scholar
PubMed
Search for other papers by S Imamura in
Google Scholar
PubMed
Search for other papers by K Yamamoto in
Google Scholar
PubMed
Search for other papers by Y Ono in
Google Scholar
PubMed
Search for other papers by M Nagata in
Google Scholar
PubMed
Search for other papers by T Kobayashi in
Google Scholar
PubMed
Search for other papers by T Kato in
Google Scholar
PubMed
Search for other papers by M Tomita in
Google Scholar
PubMed
Search for other papers by A Nakai in
Google Scholar
PubMed
Search for other papers by M Itoh in
Google Scholar
PubMed
Search for other papers by A Nagasaka in
Google Scholar
PubMed
Endothelin-1 (ET-1) concentrations are increased in patients with diabetes mellitus, particularly those with diabetic retinopathy, or essential hypertension. We hypothesized that ET-1 might participate in the development and progression of diabetic microangiopathy. In this study, the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril maleate, on diabetic angiopathy were examined in streptozotocin (STZ)-induced diabetic (STZ-DM) rats by monitoring variations in renal function and ET-1 concentrations in blood and organ tissues. Significant increases in kidney weight and in concentrations of urinary albumin, N-acetyl-fl-d-glucosamidase (NAG) and serum ET-1 were observed in the STZ-DM rats as compared with the non-diabetic rats, and the concentration of ET-1 in the kidneys tended to be increased. Microscopic and electron microscopic analyses showed increased mesangial cell proliferation, matrix expansion and enlarged mesangial area in the kidney of the diabetic rats. After administration of the ACE inhibitor, increased concentrations of urinary albumin and NAG in the STZ-DM rats were reduced to the control values with a slight improvement in the electron microscopic changes. These data suggest that ET-1 may be involved in the development and progression of diabetic nephropathy and may explain, in part, why diabetes is liable to complicate hypertension. ACE inhibitor may help to restore diabetic nephropathy in the STZ-induced diabetic rats.
Search for other papers by T Mano in
Google Scholar
PubMed
Search for other papers by K Iwase in
Google Scholar
PubMed
Search for other papers by Y Sawai in
Google Scholar
PubMed
Search for other papers by N Oda in
Google Scholar
PubMed
Search for other papers by Y Nishida in
Google Scholar
PubMed
Search for other papers by T Mokuno in
Google Scholar
PubMed
Search for other papers by Y Itoh in
Google Scholar
PubMed
Search for other papers by M Kotake in
Google Scholar
PubMed
Search for other papers by R Masunaga in
Google Scholar
PubMed
Search for other papers by A Nakai in
Google Scholar
PubMed
Search for other papers by T Tujimura in
Google Scholar
PubMed
Search for other papers by A Nagasaka in
Google Scholar
PubMed
Search for other papers by H Hidaka in
Google Scholar
PubMed
Abstract
To investigate the effect of thyroid hormone on cardiac muscle dysfunction in hyper- and hypothyroid states, we evaluated cyclic 3′, 5′-nucleotide metabolism by measuring cyclic 3′, 5′-nucleotide phosphodiesterase activity and calmodulin concentrations in the cardiac muscles of hyper- and hypothyroid rats.
Cyclic AMP (cAMP) concentration was significantly high in the cardiac muscle of hyperthyroid rats and low in that from hypothyroid rats compared with control rats. Cyclic AMP and cyclic GMP phosphodiesterase activities were significantly decreased in the soluble fraction of cardiac muscle from hyperthyroid rats and markedly increased in this fraction in hypothyroid rats compared with normal animals. Calmodulin concentration was high in hyperthyroid and low in hypothyroid rats.
It was concluded from these findings that low cAMP-phosphodiesterase activity might, in part, bring about the high concentration of cAMP. Calmodulin was sigificantly high in the cardiac muscle of hyperthyroid rats and the reverse was the case in hypothyroid rats compared with normal rats. The implication is that, in hyper- and hypothyroid states, these changes may play an important role in cardiac function via their effect on cyclic nucleotide and Ca2+ metabolism.
Journal of Endocrinology (1994) 143, 515–520
Search for other papers by H. Imura in
Google Scholar
PubMed
Search for other papers by Y. Kato in
Google Scholar
PubMed
Search for other papers by Y. Nakai in
Google Scholar
PubMed
Search for other papers by K. Nakao in
Google Scholar
PubMed
Search for other papers by I. Tanaka in
Google Scholar
PubMed
Search for other papers by H. Jingami in
Google Scholar
PubMed
Search for other papers by T. Koh in
Google Scholar
PubMed
Search for other papers by T. Yoshimasa in
Google Scholar
PubMed
Search for other papers by T. Tsukada in
Google Scholar
PubMed
Search for other papers by M. Suda in
Google Scholar
PubMed
Search for other papers by M. Sakamoto in
Google Scholar
PubMed
Search for other papers by N. Morii in
Google Scholar
PubMed
Search for other papers by H. Takahashi in
Google Scholar
PubMed
Search for other papers by K. Tojo in
Google Scholar
PubMed
Search for other papers by A. Sugawara in
Google Scholar
PubMed
ABSTRACT
Advances in techniques in molecular biology have facilitated the research into endogenous opioids and related peptides in several ways. The organization and expression of genes and the primary structure of three precursor proteins of opioid peptides have been elucidated. These studies predicted the presence of potentially bioactive peptides, which has been confirmed by later studies. Advances in techniques in protein chemistry have helped to elucidate the distribution and molecular forms of endogenous opioids and related peptides in the body, and the processing of precursor proteins. Studies on the function of these peptides have shown a broad spectrum of actions. Leumorphin, a newly identified peptide, has been shown to exhibit unique biological activities. In spite of extensive studies, the physiological and pathophysiological significance of opioid peptide systems are not yet completely understood. This is mainly due to the paucity of our knowledge about opioid receptors. Further studies on the subtypes of opioid receptors will help to elucidate all aspects of the function of endogenous opioids and related peptides.
J. Endocr. (1985) 107, 147–157
Search for other papers by T Mano in
Google Scholar
PubMed
Search for other papers by K Iwase in
Google Scholar
PubMed
Search for other papers by I Yoshimochi in
Google Scholar
PubMed
Search for other papers by Y Sawai in
Google Scholar
PubMed
Search for other papers by N Oda in
Google Scholar
PubMed
Search for other papers by Y Nishida in
Google Scholar
PubMed
Search for other papers by T Mokuno in
Google Scholar
PubMed
Search for other papers by M Kotake in
Google Scholar
PubMed
Search for other papers by A Nakai in
Google Scholar
PubMed
Search for other papers by N Hayakawa in
Google Scholar
PubMed
Search for other papers by R Kato in
Google Scholar
PubMed
Search for other papers by A Nagasaka in
Google Scholar
PubMed
Search for other papers by H Hidaka in
Google Scholar
PubMed
Abstract
Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases remains unclear, but several findings suggest that the catecholamine-β-receptor-cAMP system or other messenger systems are disturbed in these diseases. In this context, we evaluated changes in the cyclic 3′,5′-nucleotide metabolic enzyme, cyclic 3′,5′-nucleotide phosphodiesterase (PDE) and calmodulin concentrations in skeletal muscles of hyper- and hypothyroid rats.
Activities of cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats, and calmodulin concentration was high in hyperthyroid and low in hypothyroid rats, as compared with normal rats. DE-52 column chromatographic analysis showed that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in hyperthyroid rats, but the activities in peaks I and II were unchanged. These findings indicate that cAMP and calmodulin may have some role in skeletal muscle function in the hyperthyroid state, and that cAMP and calmodulin-dependent metabolism may be suppressed in the hypothyroid state.
Journal of Endocrinology (1995) 146, 287–292
Search for other papers by T Mokuno in
Google Scholar
PubMed
Search for other papers by K Uchimura in
Google Scholar
PubMed
Search for other papers by R Hayashi in
Google Scholar
PubMed
Search for other papers by N Hayakawa in
Google Scholar
PubMed
Search for other papers by M Makino in
Google Scholar
PubMed
Search for other papers by M Nagata in
Google Scholar
PubMed
Search for other papers by H Kakizawa in
Google Scholar
PubMed
Search for other papers by Y Sawai in
Google Scholar
PubMed
Search for other papers by M Kotake in
Google Scholar
PubMed
Search for other papers by N Oda in
Google Scholar
PubMed
Search for other papers by A Nakai in
Google Scholar
PubMed
Search for other papers by A Nagasaka in
Google Scholar
PubMed
Search for other papers by M Itoh in
Google Scholar
PubMed
The deterioration of glucose metabolism frequently observed in hyperthyroidism may be due in part to increased gluconeogenesis in the liver and glucose efflux through hepatocyte plasma membranes. Glucose transporter 2 (GLUT 2), a facilitative glucose transporter localized to the liver and pancreas, may play a role in this distorted glucose metabolism. We examined changes in the levels of GLUT 2 in livers from rats with l-thyroxine-induced hyperthyroidism or methimazole-induced hypothyroidism by using Western blotting to detect GLUT 2. An oral glucose tolerance test revealed an oxyhyperglycemic curve (impaired glucose tolerance) in hyperthyroid rats (n=7) and a flattened curve in hypothyroid rats (n=7). GLUT 2 levels in hepatocyte plasma membranes were significantly increased in hyperthyroid rats and were not decreased in hypothyroid rats compared with euthyroid rats. The same results were obtained with a densitometric assay. These findings suggest that changes in the liver GLUT 2 concentration may contribute to abnormal glucose metabolism in thyroid disorders.
