Peptides (v.25, #1)

An antifungal peptide with a molecular mass of 10 kDa was isolated from fruiting bodies of the mushroom Pleurotus eryngii. The peptide, designated as eryngin, inhibited mycelial growth in Fusarium oxysporum and Mycosphaerella arachidicola. It was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and S-Sepharose. Its N-terminal sequence demonstrated some similarity to the antifungal protein from the mushroom Lyophyllum shimeiji and little resemblance to thaumatin and thaumatin-like proteins.
Keywords: Mushroom; Antifungal peptide; Fruiting bodies;

A lectin was isolated from extracts of fruiting bodies of the mushroom Xerocomus spadiceus using a procedure that involved ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose, and gel filtration by fast protein liquid chromatography on Superdex 75. The lectin was unadsorbed on DEAE-cellulose and Affi-gel blue gel and adsorbed on CM-Sepharose. The lectin was capable of eliciting an approximately four-fold stimulation of mitogenic response in murine splenocytes. The hemagglutinating activity was stable up to 60 °C, halved at 70 °C, reduced to 25% at 75 °C and dwindled to an undetectable level at 80 °C. The activity remained unaltered in the presence of various divalent (Ca2+, Mg2+, Zn2+ and Mn2+) chlorides up to a salt concentration of 10 mM except in the case of ZnCl2. FeCl3 up to a concentration of 10 mM did not affect the hemagglutinating activity of the lectin. The hemagglutinating activity of the lectin was doubled in the presence of 5 mM AlCl3 or 10 mM ZnCl2 and quadrupled in the presence of 10 mM AlCl3. The activity was reduced in the presence of HCl and NaOH. Among the large number of carbohydrates tested, only inulin was able to inhibit the hemagglutinating activity of the lectin.
Keywords: Mushroom; Lectin; Xerocomus spadiceus; Isolation;

A 12 kDa ribonuclease preferential for poly U and with much lower activity toward poly A, poly G and poly C was isolated from fresh fruiting bodies of the mushroom Pleurotus sajor-caju. A purification procedure involving ion exchange chromatography on CM-cellulose, affinity chromatography on Red-Sepharose and Heparin-Sepharose, and fast protein liquid chromatography–gel filtration on Superdex 75 was used. The ribonuclease was adsorbed on all of the first three types of chromatographic media. It exhibited some activity toward herring sperm DNA and calf thymus DNA. The ribonuclease activity was unaffected in the presence of KCl (10 and 100 mM) and NaCl (100 mM and 1 M), but was strongly inhibited by CuSO4 (0.01 and 0.1 mM) and less potently inhibited by other divalent salts including MgCl2, CaCl2, ZnCl2, ZnSO4 and FeSO4. The optimal pH was 5.5 and the ribonuclease was stable up to 60 °C for 1 h. The ribonuclease inhibited mycelial growth in the fungi Fusarium oxysporum and Mycosphaerella arachidicola with an IC50 value of 95 and 72 μM, respectively. Out of the 12 species of bacteria tested, only Pseudomonas aeruginosa and Staphylococcus aureus were inhibited in growth by the ribonuclease. Viability of the tumor cells HepG2 (hepatoma) and L1210 (leukemia) was reduced with an IC50 of 0.22 and 0.1 μM, respectively in the presence of the ribonuclease. The ribonuclease inhibited translation in a cell-free rabbit reticulocyte lysate system with an IC50 of 158 nM and 3 H -methyl-thymidine uptake by murine splenocytes with an IC50 of 65 nM.
Keywords: Ribonuclease; Mushroom; Pleurotus sajor-caju; Isolation;

In vitro and in vivo activity of antimicrobial peptides synthesized based on the insect defensin by Hisako Saido-Sakanaka; Jun Ishibashi; Eiichi Momotani; Fumio Amano; Minoru Yamakawa (19-27).
Synthetic antimicrobial 9-mer peptides were designed from the amino acid sequence of an active site of insect defensin to increase the number of positively charged amino acid residues. These peptides, RLRLRIGRR-NH2, RLLLRIGRR-NH2 and RLYLRIGRR-NH2, showed strong antimicrobial activity against bacteria and fungus. These peptides showed no growth inhibition activity against murine fibroblasts or macrophages and no hemolytic activity against rabbit erythrocytes in vitro. Furthermore, the administration of these peptides protected mice from a lethal methicillin-resistant Staphylococcus aureus (MRSA) challenge. In addition, these peptides suppressed tumor necrosis factor alpha (TNF-α) gene expression and production induced by lipopolysaccharide (LPS) or lipoteichoic acid (LTA) in murine macrophages.
Keywords: Antimicrobial peptide; Insect defensin; Chemical synthesis; MRSA; TNF-α;

Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys-8]-substituted analog by Agnes Sonnevend; Floyd C. Knoop; Mahrendra Patel; Tibor Pál; Ana Maria Soto; J.Michael Conlon (29-36).
The predicted conformation of ranatuerin-1 (SMLSVLKNLG10KVGLGFVACK20INK QC), an antimicrobial peptide first isolated from the skin of the bullfrog Rana catesbeiana, comprises three structural domains: α-helix (residues 1–8), β-sheet (residues 11–16) and β-turn (residues 20–25). Circular dichroism studies confirm significant α-helical character in 50% trifluoroethanol. Replacement of Cys-19 and Cys-25 by serine resulted only in decreased antimicrobial potency but deletion of either the cyclic heptapeptide region [residues (19–25)] or the N-terminal domain [residues (1–8)] produced inactive analogs. Substitution of the glycine residues in the central domain of the [Ser-19, Ser-25] analog by lysine produced inactive peptides despite increased α-helical content and cationicity. The substitution Asn-8→Lys gave a ranatuerin-1 analog with increased α-helicity and cationicity and increased potency against a range of Gram-positive and Gram-negative bacteria and against C. albicans but only a small increase (21%) in hemolytic activity. In contrast, increasing α-helicity and hydrophobicity by the substitution Asn-22→Ala resulted in a 3.5-fold increase in hemolytic activity. Effects on antimicrobial potencies of substitutions of neutral amino acids at positions 4, 18, 22, and 24 by lysine were less marked. Strains of pathogenic E. coli from different groups showed varying degrees of sensitivity to ranatuerin-1 (MIC between 5 and 40 μM) but [Lys-8] ranatuerin-1 showed increased potency (between 2- and 8-fold; P<0.01) against all strains. The data demonstrate that [Lys-8] ranatuerin-1 shows potential as a candidate for drug development.
Keywords: Antimicrobial peptide; Drug development; Frog skin; Ranatuerin-1;

Optimal designing of β-conglycinin to genetically incorporate RPLKPW, a potent anti-hypertensive peptide by Kunihiko Onishi; Nobuyuki Matoba; Yuko Yamada; Naomi Doyama; Nobuyuki Maruyama; Shigeru Utsumi; Masaaki Yoshikawa (37-43).
Previously, we introduced the RPLKPW sequence, a highly potent hypotensive peptide designed based on ovokinin (2–7), into three homologous sites in the soybean β-conglycinin α′ subunit by site-directed mutagenesis. The modified protein expressed in Escherichia coli reduced blood pressure of spontaneously hypertensive rats (SHRs) after oral administration at a dose of 10 mg/kg, which suggested about 30% of the introduced peptide was released in vivo. In this study amino acid residues around the RPLKPW sequence were optimized with a use of synthetic peptides to facilitate release of RPLKPW by gastrointestinal proteases. Then, fourth RPLKPW was also introduced into the extension domain of the protein. The newly modified protein, which was produced in E. coli, significantly lowered blood pressure in SHRs at a dose of 2.5 mg/kg 4 h after oral administration. Furthermore, we produced an extension domain that corresponds to residues 1–143 of the modified α′ subunit containing four RPLKPW sequences by introducing a termination codon. The minimum effective dose of the modified extension domain was 1.0 mg/kg, which is 1/2000 that of ovalbumin.
Keywords: Ovokinin; Soybean β-conglycinin; Anti-hypertensive peptide; Site-directed mutagenesis; Spontaneously hypertensive rat;

More information is needed on the physiological role of the tachykinins (TKs), especially neurokinin3-receptor (NK3) agonists, in the pancreas. In this paper we investigated and compared the effect of PG-KII (10−9 to 10−6  M), a natural NK3-receptor agonist, with that of the known secretagogues substance P (10−9 to 10−6  M), caerulein (10−11 to 10−8  M) and carbachol (10−8 to 10−5  M), on amylase secretion from dispersed pancreatic acini of the guinea pig and rat. PG-KII (10−7  M) significantly increased basal amylase release from guinea pig pancreatic acini (from 5.4±0.9% to 11.3±0.5%, P<0.05) but left basal release in the rat unchanged (6.5±0.5%). The stimulant effect of PG-KII on guinea pig acini was significantly reduced by the NK3-receptor antagonist, SR 142801 (5×10−7  M), and left unchanged by the NK1-receptor antagonist, SR 140333 (5×10−7  M). Conversely, substance P (10−7  M) significantly stimulated amylase secretion from rat and guinea pig acini (12.6±0.6% and 12.1±0.7%, P<0.05). This stimulated effect of substance P was antagonized by the NK1-receptor antagonist (5×10−7  M), but not by the NK3-receptor antagonist (5×10−7  M). The PG-KII- and substance P-evoked maximal responses were lower than those evoked by caerulein (10−9  M) (guinea pig, 19.1±1.3%; rat, 18.2±0.9%, P<0.01) and carbachol (10−5  M) (guinea pig, 23.3±1.2%; rat, 24.0±1.1%, P<0.01). The inhibitors of phospholipase C U-73122 (10−5  M), phospholipase A2 quinacrine (10−5  M), and protein tyrosine kinase genistein (10−4  M), partly but significantly inhibited PG-KII, as well as carbachol-stimulated amylase release. Coincubation of PG-KII 10−7  M with submaximal doses of caerulein (10−11 to 10−10  M) and carbachol (10−7 to 10−6  M) had an additive effect on amylase release. Pre-incubation with PG-KII (10−7  M) for 30 min significantly reduced the subsequent amylase response to PG-KII, whereas pre-incubation with caerulein 10−10  M or carbachol 10−6  M did not. These findings suggest that PG-KII directly contributes to pancreatic exocrine secretion by interacting with acinar NK3 receptors of the guinea pig but not of the rat. PG-KII signal transduction involves the intracellular phospholipase C, phospholipase A2 and protein tyrosine kinase pathways. The NK3 receptor system cooperates with the other known secretagogues in regulating guinea pig exocrine pancreatic secretion and undergoes rapid homologous desensitization.
Keywords: PG-KII; Amylase release; Isolated pancreatic acini; Guinea pig; Rat;

Release and functional role of neuropeptide Y as a sympathetic modulator in human saphenous vein biopsies by M.V Donoso; R Miranda; R Briones; M.J Irarrázaval; J.Pablo Huidobro-Toro (53-64).
Transmural electrical stimulation of the sympathetic nerve endings of human saphenous vein biopsies released two forms of NPY identified chromatographically as native and oxidized peptide. The release process is dependent on extracellular calcium, the frequency, and the duration of the stimuli. While guanethidine reduced the overflow of ir-NPY, phenoxybenzamine did not augment NPY release, but increased that of noradrenaline. Oxidized NPY, like native NPY, potentiated the noradrenaline and adenosine 5′-triphospahate-induced vasoconstriction, an effect blocked by BIBP 3226 and consonant with the RT-PCR detection of the mRNA encoding the NPY Y1 receptor. These results highlight the functional role of NPY in human vascular sympathetic reflexes.
Keywords: hNPY release; Sympathetic co-transmission; Saphenous vein biopsies; Human vascular biopsies; Vascular reflexes; Oxidized NPY; Saphenous vein biopsies; NPY neuromodulation;

Helospectin I and II evoke vasodilation in the intact peripheral microcirculation by Takaya Tsueshita; Hayat Önyükusel; Varun Sethi; Salil Gandhi; Israel Rubinstein (65-69).
Helospectin I and II, two closely related mammalian neuropeptides of the secretin/glucagons/vasoactive intestinal peptide (VIP) superfamily of peptides, are co-localized with VIP in nerve fibers surrounding vascular smooth muscle. However, the role if any, VIP receptors play in transducing the vasorelaxant effects of helospectin I and II in the intact peripheral microcirculation is uncertain. The purpose of this study was to determine whether helospectin I and II elicit vasodilation in the intact peripheral microcirculation and, if so, whether this response is mediated, in part, by VIP or pituitary adenylate cyclase activating peptide (PACAP) receptor engagement, and through local elaboration of cyclooxygenase products of arachidonic acid metabolism. Using intravital microscopy, we found that suffusion of helospectin I and II (each, 1.0 nmol) evoked potent vasodilation and of similar magnitude in the intact hamster cheek pouch microcirculation (P<0.05). Suffusion of 0.1 nmol helospectin I and II had no significant effects on arteriolar diameter. Pretreatment with VIP10–28, a VPAC1/VPAC2 receptor antagonist, or PACAP6–38, a PAC1/VPAC2 receptor antagonist, had no significant effects on helospectin I- and II-induced responses. In addition, pretreatment with indomethacin had no significant effects on helospectin I- and II-induced vasodilation. Collectively, these data indicate that helospectin I and II evoke potent vasodilation in the intact peripheral microcirculation that is not transduced by VIP or PACAP receptors nor through cyclooxygenase products of arachidonic acid metabolism.
Keywords: Vasomotor tone; Resistance arteriole; VIP; PACAP; Receptor antagonist; Eicosanoids; Indomethacin; Hamster;

The effect of CNS opioid on autonomic nervous and cardiovascular responses in diet-induced obese rats by Maria J. Barnes; K.-L.Catherine Jen; Joseph C. Dunbar (71-79).
The intracerebroventricular (i.c.v.) infusion of beta-endorphin can cause either a decrease in blood pressure in normal rats or an increase in obese rats. Diet-induced obesity is associated with an increase of hypothalamic mu opioid receptors. Since beta-endorphins act by opioid receptors, we investigated the effect of CNS mu as well as kappa opioid receptor agonist and antagonist on mean blood pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in male Wistar rats fed either a high fat (HF) (40% fat by weight) or a regular low fat (control) (4% fat by weight) diet. After a 12-week-feeding period the animals were implanted with i.c.v. cannulas and 3–5 days later they were anesthetized and instrumented to record MAP, HR and RSNA. HF rats have higher MAP and the i.c.v. injection of a mu opioid agonist (DAMGO) initially decreased the MAP and then increased MAP, HR and RSNA in the normal animals. The increase was greater in HF animals. The i.c.v. injection of the mu antagonist (β-FNA) resulted in a significantly greater decrease in MAP in HF animals. β-FNA increased the RSNA in the HF rats but decreased it in the normal rats. The kappa agonist (dynorphin) decreased MAP in normal rats followed by a return to baseline, but not in HF rats. The kappa antagonist, nor-binaltorphimine (N-BP), increased MAP and RSNA in normal rats and to a lesser extent in HF rats. These findings suggest that rats given a high fat diet have higher blood pressures and a greater mu opioid-mediated responsiveness with a greater mu opioid-mediated autonomic tone. Additionally there is a decreased kappa responsiveness and tone in the HF rats. Both these changes, increased mu and decreased kappa responsiveness could strongly contribute to the increased blood pressure in obese animals.
Keywords: Blood pressure; Opioids; Sympathetic nerve activity;

The C-terminus of murine S100A9 inhibits hyperalgesia and edema induced by jararhagin by Camila Squarzoni Dale; Luis Roberto de Camargo Gonçalves; Luiz Juliano; Maria Aparecida Juliano; Ana Maria Moura da Silva; Renata Giorgi (81-89).
The effect of a synthetic peptide (H92–G110) identical to the C-terminus of murine S100A9 (mS100A9p) was investigated on hyperalgesia and edema induced by either jararhagin or papain in the rat paw. mS100A9p not only reverted hyperalgesia and edema induced by jararhagin, but also the highest concentration induced antinociception. Hemorrhage induced by jararhagin and its hydrolytic activity were inhibited by mS100A9p. These data suggest that mS100A9p might block jararhagin-induced hyperalgesia and edema by inhibiting jararhagin catalytic activity, since papain-induced hyperalgesia and edema were not inhibited by mS100A9p.
Keywords: Hyperalgesia; Edema; Jararhagin; Papain; MRP-14; S100A9;

Endomorphin 1 (EM-1) and EM-2 have been widely reported in the cells of the central nervous system (CNS) but limited research has been done regarding their distribution in the peripheral system. The occurrence of EM-1 and -2 in the spleen as measured by RIA and their ability to mediate immune function imply a role for EMs in this area. The current study examines the localization of EM-1 and -2 in the immune cells of the spleen of male and female rats via an immunohistochemical procedure. In both genders, EM-1 and -2 immunoreactive staining was predominantly present in macrophages and B cells with minimal EM immunoreactive staining in T cells. This is the first evidence of a differential distribution of EM-1 and -2 in cells of the immune system.
Keywords: Endomorphin; Spleen; Immunohistochemistry; Macrophages; B cells; T cells; Gender;

The anti-inflammatory effect of leptin on experimental colitis: involvement of endogenous glucocorticoids by Barış Çakır; Ayhan Bozkurt; Feriha Ercan; Berrak Ç. Yeğen (95-104).
The present study was designed to compare the effect of leptin on acute colonic inflammation with that of acute stress exposure, which acts via the hypothalamic-pituitary-adrenal (HPA) axis. Sprague–Dawley rats of both sexes were administered intrarectally with acetic acid. Either leptin (10 μg/kg; i.p.) or saline was injected immediately before and 6 h after the induction of colitis. A group of rats was exposed to water avoidance stress (WAS) for 30 min at the 6th h of colitis induction. RU-486 (2 mg/kg; i.p.), a glucocorticoid receptor antagonist, was injected intraperitoneally, at 12 and 1 h before the initial leptin injection, and at 1 h before the second leptin injection or exposure to WAS. Rats were decapitated at 24 h and the distal 8 cm of the colon were removed for macroscopic and microscopic scoring, determination of tissue wet weight index (WI) and tissue myeloperoxidase activity (MPO). Acetic acid-induced colitis significantly increased macroscopic and microscopic damage scores, WI and MPO, compared to control group. Exposure to acute WAS or treatment with leptin reduced the elevations in damage scores, WI and MPO induced by colitis, but no additive inhibitory effect was observed when WAS and leptin were applied together. RU-486 treatment reversed the inhibitory effects of leptin or WAS on colonic inflammation. Our results demonstrate that exogenous leptin mimics the effects of HPA axis activation on colitis-induced inflammatory process. The results also suggest that the anti-inflammatory effect of leptin involves a tissue neutrophil-dependent mechanism and is dependent on the release of glucocorticoids.
Keywords: Hypothalamo-pituitary-adrenal axis; Water avoidance stress; ACTH; Acetic acid colitis; Myeloperoxidase activity;

Gut tissues of 2-week post-ecdysis female Locusta migratoria L. were assayed for FMRFamide-like immunoreactivity (FLI) during various feeding states using both radioimmunoassay and immunohistochemistry. The feeding states investigated were: (a) 48- and 24-h starved; (b) 5-, 30-, or 60-min post-feeding initiation; and (c) a diet of wheat grass, carrots, or apples. We determined: (1) the feeding state of a locust influences FLI in all gut tissues; (2) variations in diet appear to influence FLI in all gut tissues; (3) more than one FMRFamide-related peptide (FaRP) responds to differences in diet and state of starvation in the gut tissues; and (4) the protein poor diets (carrot and apple), in conjunction with the assertion that protein to carbohydrate ratio in the diet is the key component for nutrient balancing, suggests that FaRPs may play a role in maintaining balanced nutrient content in the locust.
Keywords: FMRFamides; Insect; Foregut; Midgut; Hindgut; Gastric caecae; RIA; RP-HPLC; Immunohistochemistry; Wheat grass; Apple; Carrot;

Octreotide ameliorates alendronate-induced gastric injury by Göksel Şener; Kübra Paskaloglu; Caner Kapucu; Sule Cetinel; Gazi Contuk; Gül Ayanoğlu-Dülger (115-121).
Alendronate causes serious gastrointestinal adverse effects. The aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue, improves the alendronate-induced gastric injury. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with octreotide (0.1 ng/kg, i.p.). On the last day, following drug administration, pilor ligation was performed and 2 h later, rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation (as assessed by malondialdehyde, MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation (37.1±3.2 nmol/g) and myeloperoxidase activity (57.6±3.7 U/g), while tissue glutathione levels (0.9±0.1 μmol/g) decreased. Treatment with octreotide prevented this damage as well as the changes in biochemical parameters (MDA: 23.4±1.3 nmol/g; MPO: 31.68 U/g; GSH: 1.5±0.1 μmol/g). Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and that octreotide ameliorates this damage by inhibiting neutrophil infiltration and reducing lipid peroxidation. Therefore, its therapeutic role as a “ulcer healing” agent must be further elucidated in alendronate-induced gastric mucosal injury.
Keywords: Alendronate; Octreotide; Lipid peroxidation; Glutathione; Myeloperoxidase;

The effects of somatostatin (SRIF) microinjected unilaterally (left or right) at a dose of 10, 50, and 100 ng into the neostriatum of male Wistar rats on exploratory behavior were studied. Unilateral injections of SRIF suppressed dose-related the exploratory activity as decreased the number of horizontal and vertical movements compared to the respective controls. The effect was more pronounced when SRIF was microinjected into the right neostriatum as compared to the left neostriatum. These findings suggest some asymmetric effects of SRIF, depending on the dose and the microinjected hemisphere.
Keywords: Somatostatin; Neostriatum; Asymmetry; Exploratory behavior; Rat;

α-Melanocyte stimulating hormone has beneficial effects on cerulein-induced acute pancreatitis by Nermina Jahovic; Serap Arbak; Özgür Tekeli; İnci Alican (129-132).
We investigated the effect of α-melanocyte stimulating hormone (α-MSH) on cerulein induced acute pancreatitis in rats. α-MSH treatment (50 μg per rat, intraperitoneally) prior to cerulein reduced the plasma amylase level, pancreatic weight, pancreatic myeloperoxidase activity and the severity of the lesions microscopically. These data suggest that α-MSH has a protective effect on cerulein-induced acute pancreatitis and this effect could be attributed, at least in part, to decreased tissue leukocyte infiltration and thus, to decreased pro-inflammatory cytokine production and/or oxygen- and nitrogen-derived reactive metabolite release.
Keywords: Pancreatitis; α-Melanocyte stimulating hormone; Neutrophils; Rat;

Expression of the beacon gene in endocrine glands of the rat by Agnieszka Ziolkowska; Marcin Rucinski; Rosa Di Liddo; Gastone G. Nussdorfer; Ludwik K. Malendowicz (133-137).
Beacon gene has been recently identified in the rat hypothalamus, and reported to be overexpressed in obese animals. This pattern of expression suggests that beacon may be involved in the functional regulation of neuroendocrine axes. Hence, we have investigated the expression of beacon in the endocrine system of the rat. Reverse transcription–polymerase chain reaction showed the expression of beacon mRNA in the hypothalamus, adenohypophysis, thyroid gland, adrenal gland, testis, ovary and pancreatic islets. Immunocytochemistry demonstrated the presence of the beacon immunoreactivity in all tissues studied, the staining being very intense in the neurons of paraventricular and supraoptic nuclei, the basophils of adenohypophysis, the parathyroid gland, adrenocortical cells, testis Leydig cells, ovary thecal, granulosa and lutein cells, and pancreatic islets. Due the fact that beacon has been included in the ubiquitin-like protein family, its widespread expression in rat endocrine tissues is not astonishing. The in vivo administration of beacon[47–73] (3.5 nmol/100 body weight) elicited within 60 min a marked decrease in the plasma concentration of ACTH, aldosterone and corticosterone, and a moderate lowering of the blood levels of testosterone and estradiol. This finding suggests that beacon exerts a negative modulatory action on the pituitary–adrenal axis and gonad secretory activity, whose physiological relevance remains, however, to be established.
Keywords: Beacon; Ubiquitin-like proteins; Hypothalamus; Endocrine glands; Rat;

Thymulin and the neuroendocrine system by Rodolfo G. Goya; Oscar A. Brown; Jean-Marie Pléau; Mireille Dardenne (139-142).
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to this molecule. After its discovery in the early 1970, thymulin was characterized as a thymic hormone involved in several aspects of intra- and extrathymic T-cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, an emerging core of information points to thymulin as a hypophysotropic peptide. Here we review the evidence supporting the hypothesis that thymulin is an important player in the hypophyso-thymic axis.
Keywords: Thymulin; Hypophysiotropic activities; Nude mouse; Aging; Dyshomeostasis; Neuroendocrine imbalances; Gene therapy;