-
Biology and Medicine of Peptide and Steroid Hormones: Special Issue for the Fifth Workshop on Peptide & Hormone Research
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
1-2
Received:
17 April 2015
Accepted:
17 April 2015
Published:
6 May 2015
-
Identification and Application of Drosophila Novel Bioactive Peptides dRYamides
Takanori Ida,
Eri Iwamoto,
Takahiro Sato,
Masayasu Kojima
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
3-7
Received:
25 March 2015
Accepted:
2 April 2015
Published:
6 May 2015
Abstract: The ligands of many orphan G protein-coupled receptors (GPCRs) remain to be identified, in both vertebrates and invertebrates, such as Drosophila melanogaster. Identification of their cognate ligands is critical for understanding the function and regulation of such GPCRs. Indeed, the discovery of bioactive peptides that bind GPCRs has enhanced our understanding of the mechanisms underlying many physiological processes. Here, we identified five endogenous ligands of the Drosophila orphan GPCRs, using functional assays and reverse pharmacological techniques. dRYamide-1 and -2 were found to be paired with the Drosophila neuropeptide Y (NPY)-like receptor (CG5811). Both dRYamide-1 and -2 contain a C-terminal RYamide. In vertebrates, RYamide motifs are found in NPY-family peptides. dRYamides were found to modulate feeding motivation in flies. These results suggest that deorphanizing the Drosophila orphan GPCRs might facilitate the elucidation of various physiological functions and identification of the ligands of orphan GPCRs in mammals.
Abstract: The ligands of many orphan G protein-coupled receptors (GPCRs) remain to be identified, in both vertebrates and invertebrates, such as Drosophila melanogaster. Identification of their cognate ligands is critical for understanding the function and regulation of such GPCRs. Indeed, the discovery of bioactive peptides that bind GPCRs has enhanced our ...
Show More
-
Physiological Functions and Pathology of Ghrelin
Takahiro Sato,
Kanae Oishi,
Takanori Ida,
Masayasu Kojima
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
8-16
Received:
25 March 2015
Accepted:
3 April 2015
Published:
6 May 2015
Abstract: Ghrelin is a peptide hormone made up of 28 amino acid residues; the N-terminal serine 3 residues is modified by octanoic acid, a medium-chain fatty acid. Ghrelin is mainly secreted by the stomach and has various effects, including growth hormone release, hyperphagia, lipid accumulation, suppression of insulin secretion, and hypotensive effects. Most of these physiological effects are indispensable functions for the maintenance of homeostasis and contribute to the onset and promotion of metabolic syndrome. Accordingly, it is important to combine etiological and pathological understanding based on the biochemistry and physiology of ghrelin, which has a characteristic structure. In this manuscript, after presenting biochemical information on ghrelin, we provide an outline of its physiological function.
Abstract: Ghrelin is a peptide hormone made up of 28 amino acid residues; the N-terminal serine 3 residues is modified by octanoic acid, a medium-chain fatty acid. Ghrelin is mainly secreted by the stomach and has various effects, including growth hormone release, hyperphagia, lipid accumulation, suppression of insulin secretion, and hypotensive effects. Mos...
Show More
-
Effects of Neurotensin and LANT-6 on Food Intake in Chicks
Keiko Masuda,
Eiko Iwakoshi-Ukena,
Tetsuya Tachibana,
Kazuyoshi Ukena
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
17-23
Received:
20 March 2015
Accepted:
24 March 2015
Published:
6 May 2015
Abstract: Neurotensin (NT) and an NT-related peptide (Lys, Asn, NT8–13; LANT-6) are produced in the chicken brain and intestine, and these peptides are encoded by the same precursor gene (NT/LANT-6 precursor). Although it has been reported that the central administration of NT suppresses food intake in mammals, the effect of NT and LANT-6 on feeding behavior in birds has not yet been investigated. In this paper, we analyzed the expression levels of NT/LANT-6 precursor and the NT receptor (NTR1) mRNAs in the hypothalamic infundibulum, an important region for regulating feeding behaviors. We also examined the effects of NT and LANT-6 administration on food intake in chicks. Real-time PCR analysis showed that NT/LANT-6 precursor and NTR1 mRNAs had moderately high expression in the hypothalamic infundibulum. Further, in the hypothalamic infundibulum, the mRNA level of NT/LANT-6 precursor showed a trend toward increasing during postnatal development and increased 2.9-fold after a 48 hour fast, although the NTR1 mRNA level was not changed in both analyses. Contrary to our expectations, central administration of NT or LANT-6 had no effect on food intake in chicks.
Abstract: Neurotensin (NT) and an NT-related peptide (Lys, Asn, NT8–13; LANT-6) are produced in the chicken brain and intestine, and these peptides are encoded by the same precursor gene (NT/LANT-6 precursor). Although it has been reported that the central administration of NT suppresses food intake in mammals, the effect of NT and LANT-6 on feeding behavior...
Show More
-
Restraint-Induced Glucocorticoid Receptor Downregulation is Dysregulated in High Fat Diet-Fed Rats Likely from Impairment of miR-142-3p Expression in the Hypothalamus and Hippocampus
Takahiro Nemoto,
Yoshihiko Kakinuma,
Tamotsu Sibasaki
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
24-30
Received:
25 February 2015
Accepted:
25 March 2015
Published:
6 May 2015
Abstract: High fat diet (HFD) induces dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. The HPA axis is controlled by the feedback of glucocortioids on the hypothalamus, hippocampus and pituitary. At least three miRNAs (miR-101a, miR-124, miR-142-3p) have been reported to suppress glucocorticoid receptor (GR) translation. Because their relation to stress-induced downregulation of GR expression and dysregulation of its expression in HFD feeding are unclear, we studied to identify which miRNAs are involved in restraint-induced downregulation of GR expression in the hypothalamus and hippocampus, and to compare the basal and restraint-modified miRNA expressions in these tissues in HFD-fed rats. Rats exposed to HFD were divided into two groups, HFD-induced obese (HFD-ob) and obesity resistant (HFD-obR) rats. Basal plasma corticosterone concentrations were higher in HFD-ob than in standard chow-fed (SC) rats and in HFD-obR. Restraint-induced elevation of plasma corticosterone was higher in HFD-obR than in the other groups. Restraint decreased GR expressions and increased miR-142-3p expression in the hypothalamus and hippocampus without affecting others expressions. miR-142-3p expressions in both areas were increased by dexamethasone and restraint-induced miR-142-3p expression was blocked in adrenalectomy. The basal expression of GR or miR-142-3p expression in both areas of HFD-fed rats did not differ from those of SC, and restraint induced no changes in GR or miR-142-3p expression in both areas in HFD-ob and HFD-obR. These results suggest that impairment of glucocorticoid-induced increase in miR-142-3p may be involved in dysregulation of stress-induced downregulation of GR expression in the hypothalamus and hippocampus of HFD-fed rats.
Abstract: High fat diet (HFD) induces dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. The HPA axis is controlled by the feedback of glucocortioids on the hypothalamus, hippocampus and pituitary. At least three miRNAs (miR-101a, miR-124, miR-142-3p) have been reported to suppress glucocorticoid receptor (GR) translation. Because their...
Show More
-
Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases
Nobuo Suzuki,
Masanori Somei,
Azusa Seki,
Toshio Sekiguchi,
Yoshiaki Tabuchi,
Hiroyuki Mishima,
Yoichi Kase,
Atsushi Kaminishi,
Koji Yachiguchi,
Kei-ichiro Kitamura,
Yuji Oshima,
Kazuichi Hayakawa,
Sachiko Yano,
Atsuhiko Hattori
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
31-38
Received:
16 February 2015
Accepted:
24 March 2015
Published:
6 May 2015
Abstract: We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone in osteoblasts and osteoclasts were similar to those in mammals. Therefore, our fish scale in vitro assay system is suitable for the screening of potential bone-forming compounds. In an attempt to develop molecules that increase bone mass, novel tryptophan derivatives were synthesized and screened for effects on osteoblasts and osteoclasts using the fish scale model. As a result, novel tryptophan derivatives with the ability to possibly increase bone formation were identified, but they had no effect on osteoclast activity. Among the identified derivatives, (S)-(+)-N-acetyl-2,4,6-tribromo-5-methoxytryptophan methyl ester (BTryp) had the strongest activity on osteoblasts. The effect of this chemical on bone formation was confirmed in an ovariectomized (OVX) rat model of post-menopausal osteoporosis. Our data indicated that both trabecular bone mineral density and stress-strain index of the femoral metaphysis of BTryp-treated OVX rats were significantly higher than those of OVX rats. This study identified a bromotryptophan derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.
Abstract: We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone...
Show More
-
Effect of Adrenomedullin Administration in Two Rat Models of Experimental Inflammatory Bowel Disease
Sayaka Nagata,
Tomomi Hikosaka,
Kazuo Kitamura
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
39-42
Received:
29 March 2015
Accepted:
8 April 2015
Published:
6 May 2015
Abstract: Adrenomedullin (AM) is a novel hypotensive peptide that also exerts powerful anti-inflammatory effects. We recently showed that AM significantly reduces the clinical severity of acetic acid-induced colitis, an experimental model of inflammatory bowel disease (IBD) in rats. In the present study, we examined the effect of AM in two alternative rat models of IBD. We found that 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced megacolon development in the saline-treated group, but AM treatment reduced the macroscopic damage caused by TNBS. In the dextran sulfate sodium (DSS) model, treatment with AM reduced diarrhea and bloody stool scores, but did not reduce body weight. Histological analysis revealed that in both the TNBS and DSS models, colon inflammation was much more severe in the saline-treated group than in the AM-treated group. These findings indicate that the anti-inflammatory properties of AM make it an effective therapeutic agent for the treatment of IBD in rats.
Abstract: Adrenomedullin (AM) is a novel hypotensive peptide that also exerts powerful anti-inflammatory effects. We recently showed that AM significantly reduces the clinical severity of acetic acid-induced colitis, an experimental model of inflammatory bowel disease (IBD) in rats. In the present study, we examined the effect of AM in two alternative rat mo...
Show More
-
Characterization of Inflammatory Gene Expression and Chemotaxis of Macrophages Expressing Guanylin and Guanylyl Cyclase-C
Kazuya Hasegawa,
Sayaka Akieda-Asai,
Yukari Date
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
43-47
Received:
29 March 2015
Accepted:
9 April 2015
Published:
6 May 2015
Abstract: Depending upon the environment, macrophages can show at least two different phenotypes, including the inflammatory (M1) phenotype and the anti-inflammatory (M2) phenotype. CD11c–positive M1 macrophages produce proinflammatory cytokines such as interleukin (IL) 1β, IL-6, tumor necrosis factor α, and monocyte chemoattractant protein (MCP) 1, which are linked to the development of obesity-associated insulin resistance. Recently, we showed that double-transgenic (dTg) rats overexpressing guanylin (Gn) and its receptor, guanylyl cyclase-C (GC-C), specifically in macrophages did not become obese even when fed a high-fat diet. In the present study, to characterize macrophages expressing Gn and GC-C (i.e., Gn/GC-C macrophages), we analyzed the expression of the M1 and M2 markers of peritoneal macrophages isolated from dTg and wild type (WT) rats. We also examined the chemotaxis of these macrophages after incubation with MCP-1 or fatty acids. The expression of CD11c, an M1 macrophage marker were expressed at a significantly lower level in the peritoneal macrophages of dTg rats than in those of wild-type (WT) rats. In addition, the expression of IL-1, MCP-1 and chemokine receptor 2 were expressed at a significantly lower level in the peritoneal macrophages of dTg rats than in those of WT rats. On the other hand, there were no significant differences in the expression of M2 markers such as CD206, IL10, and arginine 1 between dTg and WT rats. We also found that the chemotaxis of Gn/GC-C macrophages incubated with fatty acids significantly increases compared to the macrophages of WT rats. Our results suggest that the low levels of proinflammatory cytokines and M1 markers in Gn/GC-C macrophages at least in part contribute to the anti-obese phenotype of Gn/GC-C Tg rats. In addition, the accelerated chemotaxis of Gn/GC-C macrophages in response to fatty acids suggests that these macrophages can uniquely react to excess fatty acids.
Abstract: Depending upon the environment, macrophages can show at least two different phenotypes, including the inflammatory (M1) phenotype and the anti-inflammatory (M2) phenotype. CD11c–positive M1 macrophages produce proinflammatory cytokines such as interleukin (IL) 1β, IL-6, tumor necrosis factor α, and monocyte chemoattractant protein (MCP) 1, which ar...
Show More
-
STARD3/MLN64 is Striving at Membrane Contact Sites: Intracellular Cholesterol Trafficking for Steroidogenesis in Human Placental Cells
Atsuki Nara,
Tohru Komiya
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
48-52
Received:
29 March 2015
Accepted:
22 April 2015
Published:
6 May 2015
Abstract: Steroid hormone synthesis begins with the conversion of cholesterol into pregnenolone by the enzyme cytochrome P450scc in mitochondria. The cholesterol used to synthesize pregnenolone is derived mainly from endocytosed LDL cholesterol. How this LDL cholesterol is transported to mitochondria in the human placenta is not well understood. Recent work has focused on how STARD3/MLN64 controls cholesterol trafficking. The STARD3 protein has a START domain that associates with cholesterol. Why STARD3 is distributed mainly to late endosomes but not to mitochondria is an obstacle to understanding the early steps in steroidogenesis. STARD3 can bind the ER protein VAP and contribute to ER-late endosome MCS formation. In this review, recent progress on STARD3 functions suggests possible models to explain how cholesterol could transit to mitochondria via MCS.
Abstract: Steroid hormone synthesis begins with the conversion of cholesterol into pregnenolone by the enzyme cytochrome P450scc in mitochondria. The cholesterol used to synthesize pregnenolone is derived mainly from endocytosed LDL cholesterol. How this LDL cholesterol is transported to mitochondria in the human placenta is not well understood. Recent work ...
Show More
-
Steroid Hormones as Transporters to Carry Exogenous Macromolecules into the Target Cell Nuclei in Vivo
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
53-57
Received:
29 January 2015
Accepted:
1 April 2015
Published:
6 May 2015
Abstract: Upon injection into the vascular system of rats, testosterone-bovine serum albumin conjugate (testosterone-BSA) is taken up by cells via the process of endocytosis. When it is taken up by the target cells of testosterone such as spermatogenic cells, it enters the nuclei of the cells. However, testosterone-BSA does not enter the nuclei of the non-target cells such as hepatocytes and thymocytes. Similarly, hydrocortisone-BSA conjugate enters the nuclei of its target cells such as hepatocytes and thymocytes. In the vesicular trafficking of testosterone-BSAs into the nucleoplasm, the vesicle membrane is likely to fuse with a nuclear hemifusion diaphragm. IgG coupled with hydrocortisone also enters the hormone-target cell nuclei, with its antigenicity kept intact. These results suggest that steroid hormones could act as transporters for conveying exogenous macromolecules into the target cell nuclei in vivo. Our studies provide a novel insight to the functions of steroid hormones.
Abstract: Upon injection into the vascular system of rats, testosterone-bovine serum albumin conjugate (testosterone-BSA) is taken up by cells via the process of endocytosis. When it is taken up by the target cells of testosterone such as spermatogenic cells, it enters the nuclei of the cells. However, testosterone-BSA does not enter the nuclei of the non-ta...
Show More
-
Overviews of Stem Cells for Gonadal and Adrenal Steroidogenic Cells
Takashi Yazawa,
Yoshitaka Imamichi,
Kaoru Miyamoto,
Junsuke Uwada,
Md Rafiqul Islam Khan,
Takanobu Taniguchi
Issue:
Volume 3, Issue 3-2, May 2015
Pages:
58-64
Received:
29 March 2015
Accepted:
31 March 2015
Published:
6 May 2015
Abstract: Gonads and adrenal glands are the primary organs for the production of steroid hormones in mammals. Steroid hormones play important roles in development and are essential for the maintenance of homeostasis during adult life. To supply sufficient amounts of hormones, gonads and adrenal glands maintain their functions by replenishment of steroidogenic cells. It has been hypothesized that stem/progenitor cells of steroidogenic cells are important for this phenomenon. In fact, such cells have been recently identified in gonads and adrenal glands. However, steroid hormone production decreases progressively with age, causing problems such as menopausal disorders in women. Although steroid hormones are administered to these patients, induction of steroidogenic cells from stem cells is a potential strategy to prevent menopausal disorders. Here, we review the current knowledge on stem cells that replenish steroid hormone-producing cells in the gonads and adrenal glands. We also discuss induction of steroidogenic cells from stem cells derived from non-steroidogenic organs.
Abstract: Gonads and adrenal glands are the primary organs for the production of steroid hormones in mammals. Steroid hormones play important roles in development and are essential for the maintenance of homeostasis during adult life. To supply sufficient amounts of hormones, gonads and adrenal glands maintain their functions by replenishment of steroidogeni...
Show More
