Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C.
Proc Natl Acad Sci U S A
J A Coto, E M Hadden, M Sauro +2 more
Thymic epithelial cells (TEC) are known to secrete thymic hormones that influence maturation of T lymphocytes. One of these peptides, thymulin, requires zinc in an equimolar ratio for biological activity. A previous study [Cousins, R. J. & Leinart, A. S. (1988) FASEB J. 2, 2884-2890] showed that interleukin 1 (IL-1) in vivo stimulates zinc uptake by the thymus. Both the alpha and beta forms of IL-1, which stimulate proliferation of human TEC, also stimulate their uptake of zinc in vitro, and this latter stimulation is both dependent and independent of proliferation. Zinc induces zinc accumulation without proliferation. Two other stimulants of proliferation, bovine pituitary extract and epidermal growth factor, stimulate zinc uptake by TEC, but only in a manner dependent on proliferation. Utilizing in situ hybridization, we show that the IL-1 alpha and beta forms and zinc induce metallothionein mRNA expression TEC. Metallothionein is thought to be involved in the transfer of zinc to thymulin. IL-1 was shown to stimulate the secretion of thymulin as measured both by its ability to stimulate induction of IL-2 receptor-positive lymphocytes from human peripheral blood lymphocytes and by the azathioprine-sensitive rosette assay. In addition, the zinc-thymulin complex in the presence, but not absence, of IL-1 stimulates nuclear protein kinase C in isolated lymphocyte nuclei. IL-1 apparently regulates the synthesis or secretion and delivery of zinc-thymulin complex to the T-lymphocyte system.
Thymic endocrinology.
Int J Immunopharmacol
J W Hadden
Thymus endocrinology is characterized by the action of various hormones on the thymus endocrine milieu consisting of thymocytes, thymic epithelial cells and thymic stromal cells. Extrathymic hormonal influences include pituitary-derived hormones, such as prolactin and indirectly by ACTH via hydrocortisone from the adrenal, by thyroid-stimulating hormone (TSH) via thyroid hormones from the thyroid, and by LH and RH via sex steroids from gonads and adrenal. In addition, the thymus produces several putative thymic hormones: thymosin alpha 1, thymulin and thymopoietin, which have been reported to circulate and to act on both prothymocytes and mature T-cells in the periphery thus maintaining their commitment to the T-cell system and its functions. These endocrine influences decline with age and are associated with "thymic menopause" and cellular immune senescence contributing to the development of diseases in the aged. The intrathymic environment is characterized by a complex network of paracrine and autocrine endocrine signals involving both interleukins and thymic peptides. Thymic epithelial cells respond to IL-1 with proliferation and secretion of IL6 and GM-CSF. They similarly respond to cellular interactions with the production of IL1. Thymic epithelial cells also secrete thymic hormones, as exemplified by the zinc-thymulin complex, under stimulation with IL1 and other hormonal influences. Thymic stromal cells contribute, at minimum, IL1. These various interleukin and thymic hormone influences can be envisioned to operate in a synergistic interactive network to carry the evolving T-cell through its stepwise development to a mature T-cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Arginine-containing compounds and thymic endocrine activity.
Thymus
N Fabris, E Mocchegiani
The frequent association of malnutrition, infectious disease and aging has stressed the role played by some nutrients on the immune efficiency and particularly on the age-dependent immunological decline. Since arginine has been proven to enhance immune efficiency as demonstrated by the observation that supplemental dietary arginine accelerates would healing and increases thymus weight, we have evaluated the influence of oral administration of arginine on the age-associated immune deficiencies and in particular on the reduced thymic endocrine activity, as measured by the circulating level of one of the best known thymic peptides, i.e. thymulin. Thirty days oral treatment with arginine at the dose of 0.03 g/Kg b.w./day in 20 month old mice induces a full recovery of thymic endocrine activity and a significant increase of PHA responsiveness by spleen cells, when compared with untreated age-matched controls. In humans, oral administration of a commercially available arginine-lysin combination (Lysargin, Baldacci, Pisa, Italia) at the dose of 4 gr. of arg. + 4 gr. of Lysine induces a significant increment of thymulin blood level both in elderly and in cancer patients and at peripheral level, an increase of CD4+ lymphocyte subpopulation. These findings confirm the immunomodulation role of arginine and suggest that on the target of arginine as the thymus and particularly its endocrine activity. Furthermore arginine and arginine-containing compounds may offer a new therapeutical approach to restore thymic immunodeficiencies associated with age or secondary to pathologies inducing thymic deterioration such as trauma, stress and cancer.
Clonidine pretreatment modifies the growth hormone secretory pattern induced by short-term continuous GRF infusion in normal man.
Clin Endocrinol (Oxf)
L Lima, V Arce, M J Diaz +2 more
The aim of this study was to investigate the effect of a single dose of clonidine on the pattern of GH release in response to a 10-hour continuous GRF infusion in normal man.
Role of growth hormone-releasing hormone on pentagastrin-induced growth hormone release in normal subjects.
J Endocrinol Invest
J F Garcia-Rojas, A Mangas, A Barba +3 more
In order to investigate the mechanisms by which gastrin cause GH release in humans we measured the GH response to pentagastrin alone (1.5 micrograms/kg/hour from 120 to 210 min) and following pretreatment with GHRH (GHRH 1-29,250 micrograms, iv at 0 min) in normal male subjects. Prior GHRH administration abolished the GH response to the second bolus of GHRH (1 micrograms/kg) administered two hours later. Pentagastrin infusion induced a rise in GH levels maximal at 60 min (9.1 + 0.6 ng/ml, mean + SE), but this rise was abolished by pretreatment with GHRH. Finally, we found that gastrin did not modify basal GH release or GH responses to GHRH by rat anterior pituitary cells in monolayer culture. Taken together, these data suggest that gastrin regulates GH secretion by acting at hypothalamic level.
Effects of a chronic GRF treatment on lambs having low or normal birth weight.
Domest Anim Endocrinol
P Pastoureau, J Charrier, M M Blanchard +4 more
The effects of a long term treatment with human GRF(1-29)NH2 on plasma growth hormone (GH), somatomedin C (Sm-C), histomorphometric parameters of bone growth and body composition were investigated in normal and low birthweight male lambs. The animals were divided into two groups according to their birthweight: 24 normal birthweight (NBW) lambs weighing more than 4 kg and 22 low birthweight (LBW) lambs weighing less than 2.5 kg at birth. Half of the animals in each group received two daily subcutaneous injections (8 micrograms/kg body weight) of hGRF(1-29) NH2 (GRF) from birth to slaughter at 45 or 90 days of age. The other animals received the solvent only. At the beginning and at the end of the treatment, plasma GH and serum Sm-C concentrations were measured in all groups. After slaughter, a histomorphometric study was performed on undecalcified sections of metacarpal growth plates, and the remaining of the carcass was pulverized to study the chemical body composition. GRF induced GH release in both GRF-treated groups. However, plasma GH reached higher (P less than .001) concentrations and the GRF-induced GH peak lasted longer in LBW than in NBW lambs. At day 45, the GRF treatment increased (P less than .05) serum Sm-C concentrations in LBW. Most of histomorphometric parameters reflecting the metacarpal growth in length, were not statistically modified under GRF treatment. However, the size of degenerative cells was smaller (P less than .05) in LBW treated lambs as compared to controls. Consequently, the cell production in the growth plate was increased (P less than .05) under GRF treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Co-existence of galanin and acetylcholine: is galanin involved in memory processes and dementia?
Trends Neurosci
J N Crawley, G L Wenk
Galanin-like immunoreactivity co-exists with choline acetyltransferase-like immunoreactivity in neurons of the septal-hippocampal and nucleus basalis of Meynert-neocortical pathways. These structures mediate some forms of cognition, and characteristically degenerate in Alzheimer's disease. Biochemical, neurophysiological and behavioral studies indicate that galanin acts as an inhibitory modulator of cholinergic function. In this article, we consider the possibility of a role for galanin in memory processes and dementia.
Effects of active immunization against somatostatin on serum growth hormone concentration in growing pigs: influence of fasting and repetitive somatocrinin injections.
Endocrinology
P Dubreuil, G Pelletier, D Petitclerc +3 more
Three experiments were conducted with growing pigs actively immunized against a protein-conjugated somatostatin (SRIF) in Freund's adjuvant. In the first experiment, blood from 24-week-old pigs (seven immunized and eight control) was sampled at 20-min intervals for 6 h to evaluate basal GH concentrations. The animals were then injected iv with porcine GH-releasing factor (GRF)-(1-29)NH2 (10 micrograms/kg). Before GRF stimulation, immunized animals had higher (P less than 0.05) baseline mean GH levels (2.6 vs. 1.4 ng/ml) and area under the GH curve (AUC; 1632 vs. 779 ng/min.ml); they also had higher AUC after GRF administration (4268 vs. 1972 ng/min.ml). In a second experiment eight immunized and eight control pigs were injected iv four times at 90-min intervals with porcine GRF (10 micrograms/kg). Control pigs responding to the first injection did not respond to the second and third, and those responding to the second did not respond to the first, third, and fourth, indicating a decreased responsiveness that was longer than 3 h post-GRF response in control pigs. SRIF-immunized pigs had a more consistent GH response to the GRF injections. Overall, a reduced response was observed after the second and the fourth injections in immunized pigs, although five and six of eight animals had a GH peak response higher than 10 ng/ml during these periods. In a third experiment, effects of fasting, GRF, and SRIF immunization were studied. Immunization and fasting had their own positive effects on serum GH levels. Immunization increased baseline mean GH levels (5.0 vs. 2.2 ng/ml) and total AUC before (2318 vs. 1073 ng/min.ml) and after (1886 vs. 910 ng/min.ml) iv GRF stimulation (10 micrograms/kg) compared to controls. Fasting increased the mean baseline GH level (4.5 vs. 2.6 ng/ml), and it increased AUC before exogenous GRF stimulation (2009 vs. 1392 ng/min.ml). In conclusion, SRIF in pigs seems to be a potent GH-governing factor, since, when inhibited, baseline mean GH levels increase, and a consistent response to GRF is observed. Fasting could increase GH concentrations by different ways: decreasing SRIF release and increasing GRF release or modifying the sensitivity of the somatotrophs to both factors.
Decreased level of cardiac antioxidants in endurance-trained rats.
Acta Physiol Scand
M Kihlström, J Ojala, A Salminen
Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendo- and subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo- and subepimyocardium and Cu,Zn-superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and in the subepimyocardium. The activity of glucose-6-phosphate dehydrogenase increased in the right ventricle and in the subepimyocardium. The activity of glutathione peroxidase and the total tissue contents of carnosine and anserine and tissue sulphydryl groups remained unchanged as compared to the control group. The endurance training caused only minor changes in the regional distribution of antioxidants. The major findings were the disappearance of the difference in the activity of catalase between the right and the left ventricle and the increase in the activity of glucose-6-phosphate dehydrogenase as compared to that of the left ventricle. The results show that endurance training by swimming decreases the level of cardiac antioxidants. This decrease may be due to the increased oxygen metabolism and the subsequent increase in the formation of oxygen free radicals, which could deplete the antioxidant pool.
Thymulin, a zinc-dependent hormone.
Med Oncol Tumor Pharmacother
J F Bach, M Dardenne
Thymulin (formerly called FTS) is a well defined nonapeptide hormone produced by thymic epithelial cells. Its biological activity and antigenicity depend upon the presence of the metal zinc in the molecule. This pharmacologically active metallopeptide induces the differentiation of T-cells and enhances several functions of the various T-cell subsets in normal or partially thymus-deficient recipients. Its effect on suppressor T-cells is, so far, the most remarkable and should be the first to find useful clinical applications. The peptide is a natural hormone, available in synthetic form. It is not toxic and one may foresee its clinical use as one of the major immunoregulatory agents in the near future.
Peptide histidine isoleucine and vasoactive intestinal polypeptide cause relaxation of opossum internal anal sphincter via two distinct receptors.
Gastroenterology
S Nurko, B M Dunn, S Rattan
The purpose of this investigation was to characterize the nature of peptide histidine isoleucine (PHI) and vasoactive intestinal polypeptide (VIP) receptors, and to examine the role of PHI in internal anal sphincter (IAS) relaxation. The studies were performed on opossums anesthetized with alpha-chloralose. The pressures in the IAS were recorded using continuously perfused catheters. The IAS responses to PHI analogues, PHI-27, PHM-27, PHI-(14-27)-NH2, PHI-(1-13), to VIP, to rectal balloon distention, sacral nerve stimulation, and local intramural stimulation were evaluated before and after PHI-(14-27)-NH2, PHI tachyphylaxis, and the VIP antagonists [4 Cl-D-Phe6, Leu17] VIP (VIP analogue) and (N-Ac-Tyr1, D-Phe2)-GRF(1-29)-NH2 (growth hormone releasing factor analogue). The inhibitory responses by all of the PHI analogues and VIP were not modified by tetrodotoxin. PHI-(14-27)-NH2 and PHI tachyphylaxis caused significant antagonism of the fall in internal anal sphincter pressure by PHI-27 and PHM-27 without modifying the IAS responses to VIP and rectal balloon distention, sacral nerve stimulation, and local intramural stimulation. On the other hand, VIP and growth hormone releasing factor analogues caused significant antagonism of VIP responses without modifying the responses to PHI-27. We conclude that distinct PHI and VIP receptors are present in the IAS smooth muscle and that PHI may not play a significant role in the IAS relaxation via the rectoanal reflex.
Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.
Proc Natl Acad Sci U S A
J Mastropaolo, N S Nadi, N L Ostrowski +1 more
Galanin coexists with acetylcholine in medial septal neurons projecting to the ventral hippocampus, a projection thought to modulate memory functions. Neurochemical lesions of the nucleus basalis-medial septal area in rats impaired choice accuracy on a delayed alternation t-maze task. Acetylcholine (7.5 or 10 micrograms intraventricularly or 1 micrograms micro-injected into the ventral hippocampus) significantly improved performance in the lesioned rats. Atropine (5 mg/kg intraperitoneally or 10 micrograms intraventricularly), but not mecamylamine (3 mg/kg intraperitoneally or 20 micrograms intraventricularly), blocked this action of acetylcholine, suggesting involvement of a muscarinic receptor. Galanin (100-500 ng intraventricularly or 200 ng into the ventral hippocampus) attenuated the ability of acetylcholine to reverse the deficit in working memory in the lesioned rats. The antagonistic interaction between galanin and acetylcholine suggests that endogenous galanin may inhibit cholinergic function in memory processes, particularly in pathologies such as Alzheimer disease that involve degeneration of basal forebrain neurons.
Galanin-like immunoreactivity is unchanged in Alzheimer's disease and Parkinson's disease dementia cerebral cortex.
J Neurochem
M F Beal, R A Clevens, G K Chattha +3 more
Galanin is a recently isolated neuropeptide that is of particular interest in dementing disorders because of its known colocalization with choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in Alzheimer's disease, and there is a corresponding deficiency of cortical choline acetyltransferase activity. In the present study, galanin-like immunoreactivity was measured in the postmortem cerebral cortex and hippocampus of 10 controls and 14 patients who had had Alzheimer's disease. Significant reductions of choline acetyltransferase activity (50-60%) were found in all regions examined; however, there was no significant effect on concentrations of galanin-like immunoreactivity. Similar measurements were made in postmortem tissues of 12 control and 13 demented Parkinsonian patients who had had Alzheimer-type cortical pathology. Choline acetyltransferase activity was again significantly decreased in all regions examined but there were no significant reductions in galanin-like immunoreactivity. Experimental lesions of the fornix in rats produced parallel significantly correlated reductions of both choline acetyltransferase activity and galanin-like immunoreactivity in the hippocampus. Galanin-like immunoreactivity in the human hypothalamus consisted of two molecular-weight species on gel-permeation chromatography, and two forms were resolved by reverse-phase HPLC. The paradoxical preservation of galanin-like immunoreactivity, despite depletion of the activity of choline acetyltransferase, with which it is colocalized, is as yet unexplained. Recent studies have shown that galanin inhibits both acetylcholine release in the hippocampus and memory acquisition; therefore, preserved galanin may exacerbate the cholinergic and cognitive deficits that accompany dementia.
Serum thymulin in human zinc deficiency.
J Clin Invest
A S Prasad, S Meftah, J Abdallah +4 more
The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions.
Influence of dopaminergic, adrenergic and cholinergic blockade and TRH administration on GH responses to GRF 1-29.
Clin Endocrinol (Oxf)
V Jordan, C Dieguez, I Lafaffian +4 more
In order to establish the influence of dopaminergic, alpha-adrenergic and cholinergic pathways on GRF-mediated GH release we have studied the GH responses to GRF 1-29 (100 or 50 micrograms as i.v. bolus) alone and in combination with metoclopramide (MCP, 10 mg, i.v.), thymoxamine (THYM, 210 micrograms/min, 150 min infusion), and atropine (1.2 mg, i.v.). We have also investigated any possible interaction between TRH and GRF in view of the reported inhibitory effects of TRH infusion on stimulated GH release. Dopaminergic and alpha-adrenergic blockade with MCP and THYM respectively, did not have any effect on the GH responses to GRF. This lack of effect strongly suggests that any action which these neurotransmitters may exert on GH secretion is not at a pituitary level. TRH did not modify the GH response to GRF suggesting that the inhibitory effect on stimulated GH secretion is exerted at a hypothalamic level. In contrast, GH responses to GRF were significantly reduced by prior administration of atropine. These data support the view that cholinergic pathways play an important role in the regulation of GH secretion and such control may be exerted at both hypothalamic and pituitary levels.
Interaction of growth hormone-releasing factor (GRF) and 14 GRF analogs with vasoactive intestinal peptide (VIP) receptors of rat pancreas. Discovery of (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 as a VIP antagonist.
Endocrinology
M Waelbroeck, P Robberecht, D H Coy +3 more
Adenylate cyclase stimulation by GH-releasing factor (GRF) and 14 GRF analogs (modified in the N-terminal part) was compared to the capacity of the same peptides to inhibit [125I]iodo-vasoactive intestinal peptide (VIP) binding in rat pancreatic plasma membranes. These peptides interfered with VIP receptors as they inhibited [125I]iodo-VIP binding, and probably acted through VIP-preferring receptors as one of these peptides [(N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2] selectively inhibited both VIP- and GRF-stimulated adenylate cyclase activities. In general, alterations in positions 6 and 7 (but not in positions 1-4) markedly reduced the affinity of the resulting GRF analog [based on Kact (concentration exerting half-maximal stimulation) values]. The intrinsic activity exerted by GRF analogs on adenylate cyclase was reduced by acetylation of the free NH2 group and by the replacement of Asp3, Ala4, Phe6, and Thr7 by the corresponding D-isomer. The presence of pCl-Phe6 and Trp6 also depressed this parameter. Substitution in GRF (or its N-acetylated derivative) by D-Phe2, D-Arg2, and D-Ala4 again reduced the intrinsic activity, whereas substitution of the natural L-amino acid residue by D-Ala2 and Phe4 gave superagonists.