Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the content of substance P and TRH in the lumbar segment of the rat spinal cord were studied. The peptide content of discrete spinal cord regions removed by punches of frozen serial slices was measured by RIA. Animals receiving T4 replacement therapy were indistinguishable from normal littermates. In hypothyroid animals without PCPA-treatment, levels of TRH and substance P were significantly increased by 100% in the ventral and the dorsal lumbar spinal cord, respectively. Inhibition of serotonin biosynthesis by PCPA increased by 90% the substance P content in the dorsal horn of euthyroid rats and abolished completely the stimulatory effect of hypothyroidism on the TRH content of the ventral horn. These findings suggest the existence of a physiological relationship between substance P and TRH with the serotoninergic system in the rat spinal cord and that thyroid hormone is implicated in the normal development of the peptide-containing neurons in the rat spinal cord.
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PMID:Comparative effects of neonatal hypothyroidism and euthyroidism on TRH and substance P content of lumbar spinal cord in saline and PCPA-treated rats. 619 82

The effects of substance P (SP), angiotensin II, oxotremorine and prostaglandin D2 (PG D2) on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion in rats were studied. Either SP (100 micrograms/kg), angiotensin II (500 micrograms/kg), oxotremorine (1.0 mg/kg) or PGD2 (500 micrograms/kg) was injected intravenously or intraperitoneally, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by means of a specific radioimmunoassay for each. The hypothalamic immunoreactive TRH (ir-TRH) contents were significantly increased by oxotremorine or SP and significantly decreased by angiotensin II, but no by PG D2. The plasma ir-TRH concentrations were significantly increased by angiotensin II, but not by oxotremorine, SP or PG D2. The plasma TSH levels were significantly increased by angiotensin II and significantly decreased by oxotremorine, SP or PG D2 in a dose-related manner. The plasma ir-TRH and TSH responses to cold were inhibited by oxotremorine, SP or PG D2, but enhanced by angiotensin II. The plasma TSH response to TRH was inhibited by SP, but enhanced by angiotensin II. The plasma TSH response to TRH did not differ from that of the control after PG D2 injection. In the haloperidol- or para-chlorophenylalanine (PCPA)-pretreated group, the inhibitory effect of PG D2 or oxotremorine on TSH release was prevented, while in the L-DOPA- or 5-hydroxytryptophan (5-HTP)-pretreated group, the inhibitory effect of SP on TSH release was prevented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of substance P, angiotensin II, oxotremorine and prostaglandin D2 on thyrotropin secretion in rats. 620 27

There is extensive deiodinative metabolism of thyroxine (T4) in thyroid hormone target organs, including the pituitary and brain. In both rat and man, most of the 3,3',5-triiodothyronine (T3) in the body is produced outside the thyroid gland by deiodination of T4. T3 is the principal active form of thyroid hormone within cells. In the rat, there are at least three enzymatic iodothyronine-deiodinating pathways which can be distinguished by kinetics and substrate and inhibitor specificities. Two of these (types I and II) can convert T4 to T3. The third pathway (type III) converts T4 to the inactive reverse-T3 and T3 to an inactive diiodothyronine. Both the anterior pituitary and the brain produce most of their intracellular T3 locally, by the type-II pathway. Type-III activity is present throughout the brain, but not in the anterior pituitary. Studies in the rat, using the deiodination inhibitor iopanoic acid, show that the capacities of T4 to inhibit thyrotropin release and stimulate growth hormone synthesis require conversion of T4 to T3 in the pituitary. Studies in man strongly suggest that the same is true in the human adenohypophysis, and a syndrome in man of a deficiency in this process possibly exists. The hypothalamus exhibits some responses to thyroid hormone, including changes in somatostatin and substance P content and changes in activities of type-II and III deiodination. The mechanism(s) of action of thyroid hormone in the hypothalamus, and in the brain in general, are not yet well understood.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of thyroid hormone deiodination in the regulation of hypothalamo-pituitary function. 637 72

Since VIP occurs in intrathyroidal nerves its role in thyroid hormone secretion has been investigated. It has been found that VIP is a stimulator of iodothyronine secretion in mice. In this respect VIP has a weaker potency than TSH, but shows a similar time characteristic. Also, VIP and TSH potentiate each others effects. In contrast to the effect of TSH, that of VIP is uninfluenced by alpha-adrenoceptor blockade. VIP, like TSH, stimulates thyroid cyclic AMP production. Thus, VIP nerves might, together with TSH, adrenergic and cholinergic nerves and other peptides such as somatostatin, participate in the complex regulation of iodothyronine secretion. Beside this, VIP has also been found to stimulate calcitonin secretion in rats. Other intrathyroidal neuropeptides, such as substance P and CCK-4, have been found to be without effects on iodothyronine secretion, but, like VIP, to stimulate calcitonin secretion.
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PMID:Influence of VIP on thyroid hormone secretion. 647 58

The effect of peptide and nonpeptide substance P antagonists on prolactin (PRL) and growth hormone (GH) secretion was evaluated in three-dimensional rat anterior pituitary cell aggregates. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P inhibited basal growth hormone (GH) release at a concentration range of 1-10 microM. At higher concentrations (50 microM), the analogue inhibited basal prolactin (PRL) release but provoked a tenfold stimulation of GH release. However, these latter two effects could neither be mimicked nor antagonized by the tachykinins substance P (10 microM), neurokinin A (10 microM), and neurokinin B (3.3 microM). The effects could also not be explained by agonism or antagonism at the level of other receptors (e.g., vasopressin, bombesin, angiotensin II, thyroid hormone-releasing hormone, vasoactive intestinal peptide, dopamine, adrenaline, acetylcholine). Remarkably the nonpeptide substance P antagonists R 30732 (10 microM), R 32602 (10 microM), and CP-96,345 (10 microM) showed a similar inhibition of PRL release and a stimulation of GH release. At a one hundredfold lower concentration, sufficient to block substance P receptors in other tissues. CP-96,345 did not affect PRL or GH release. It is concluded that substance P antagonists, when used at high concentrations, have profound intrinsic activities on PRL and GH release that are not mediated by substance P receptors. The failure of the more potent substance P antagonist, CP-96,345, to influence basal PRL or GH release when used at lower concentrations suggests that endogenous substance P in the anterior pituitary does not play a tonic paracrine role on GH or PRL secretion.
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PMID:Unexpected effects of peptide and nonpeptide substance P receptor antagonists on basal prolactin and growth hormone release in vitro. 768 Jan 28

The evidence for the integration of the submandibular gland (SMG) into the neuroimmunoregulatory network has been reviewed. In laboratory rodents, factors extracted from the SMG were shown to stimulate lymphocyte proliferation, to affect the weight of the thymus, spleen and lymph nodes and to induce immunosuppression in several in vivo animal models. The SMG produces significant quantities of nerve growth factor (NGF), epidermal growth factor (EGF), transforming growth factor-beta and kallikreins, which are secreted into the saliva and affect immune and mucosal tissues and nerve endings in the gastrointestinal tract. These factors play a role in regulating mucosal immuno/inflammatory response and in regeneration and healing. The major salivary glands also produce antimicrobial proteins and secretory IgA antibodies which are essential factors in mucosal host defense. SMG-derived NGF, EGF and glandular kallikrein are delivered into the bloodstream where they may act as important systemic immunoregulators and also have major regulatory influences on the central neuroendocrine system. There is evidence to indicate that EGF is involved in the regulation of gonadal function. Growth hormone, prolactin, androgens, thyroid hormone and corticosteroids regulate protein synthesis in the SMG, whereas secretory activity is regulated by sympathetic (alpha- and beta-adrenergic) parasympathetic (muscarinic) and peptidergic (substance P and vasoactive intestinal peptide) nerve fibers. Fluid and electrolyte secretion is promoted by parasympathetic, whereas protein secretion is stimulated by sympathetic nerve impulses. Steroid hormones and cytokines (interleukin-1 alpha, -beta, tumor necrosis factor, interferon-gamma) have a major regulatory influence on protein secretion, including the secretion of immunoglobulin into the saliva. The SMG interacts with the mucosal and systemic compartments of the immune system, with the central and peripheral nervous systems, with the pituitary gland, and with peripheral endocrine organs. These interactions enable the SMG to exert regulatory influences on immune/inflammatory reactions in the gastrointestinal tract, in the lungs, and possibly elsewhere. It is suggested that these functions make this gland a key regulatory organ in the neuroimmunoregulatory network. Evidence is increasing that the major salivary glands fulfill similar functions in other species, including humans.
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PMID:The submandibular gland: a key organ in the neuro-immuno-regulatory network? 896 48

Altered thyroid statuses are associated with autonomic disorders. Medullary thyrotropin-releasing hormone (TRH) and substance P (SP) regulate autonomic nervous activity. The influences of thyroid statuses on TRH and SP gene expressions in the caudal raphe nuclei and the parapyramidal regions were studied using quantitative in situ hybridization histochemistry. In male rats thyroidectomized (Tx) for 30 days, the serum T4 levels decreased by 64% and the medullary pro-TRH mRNA signals (silver grains per neuron) significantly increased by 32-45%. These changes were prevented by daily i.p. T4 (2 microg/100 g) injection in Tx rats. In sham operated/T4 (20 microg/100 g, daily) injected rats, T4 levels significantly increased by 88% and the silver grains decreased by 38-40%. Medullary SP mRNA signals were not significantly changed by altering thyroid status. These results support the concept that thyroid hormone regulates medullary TRH gene expression by negative feedback.
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PMID:Hyperthyroidism decreases thyrotropin-releasing hormone gene expression in the caudal raphe nuclei and the parapyramidal regions in rats. 1061 37

We have investigated with histochemical techniques the expression of peptides and other neurochemical markers in the hypothalamus and olfactory bulb of male mice, in which the genes encoding the alpha and beta thyroid hormone receptors (TRalpha1, TRbeta1 and TRbeta2) have been deleted. Thyrotropin-releasing hormone messenger RNA levels were increased in the hypothalamic paraventricular nucleus and in the medullary raphe nuclei of mutant mice lacking the thyroid hormone receptors alpha1 and beta (alpha1(-/-)beta(-/-)), as compared to wild-type mice. In contrast, galanin messenger RNA levels were lower in the hypothalamic paraventricular nucleus of mutant animals, as was galanin-like immunoreactivity in the internal layer of the median eminence. Substance P messenger RNA levels were unchanged in the medullary raphe nuclei. Thyrotropin-releasing hormone receptor messenger RNA levels were increased in motoneurons, unchanged in the subiculum, and lower in the amygdala of mutant animals. Galanin messenger RNA levels were unchanged in the hypothalamic dorsomedial and arcuate nuclei of the thyroid hormone receptor alpha1(-/-)beta(-/-) mice, as was the immunocytochemistry for oxytocin and for vasopressin in the hypothalamic paraventricular nucleus. A reduction in tyrosine hydroxylase messenger RNA levels was found in the arcuate nucleus of mutant mice. In the olfactory bulb, immunohistochemistry for calbindin and for tyrosine hydroxylase revealed a reduction in the intensity of labeling of nerve processes in the glomerular layer of thyroid hormone receptor alpha1(-/-)beta(-/-) mice. The tyrosine hydroxylase messenger RNA levels were also slightly reduced. In contrast, the levels of galanin and neuropeptide Y messenger RNA in this region were unchanged in thyroid hormone receptor alpha1(-/-)beta(-/-) mice as compared to wild-type mice. Together these studies reveal many regional and neurochemically selective alterations in neuronal phenotype of mice devoid of all known thyroid hormone receptors.
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PMID:Expression of peptides and other neurochemical markers in hypothalamus and olfactory bulb of mice devoid of all known thyroid hormone receptors. 1111 49

Human growth is a complex process starting at conception and completing in adolescence at the time of growth plate fusion. Growth can be divided into four phases: (1) fetal, where the predominant endocrine factors controlling growth are insulin and the insulin-like growth factors. (2) Infancy, where growth is mainly dependent upon nutrition. (3) Childhood, where the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis and thyroid hormone are most important. (4) Puberty, where along with the GH-IGF-I axis the activation of the hypothalamo-pituitary-gonadal axis to generate sex steroid secretion becomes vital to the completion of growth. GH is released from the pituitary in a pulsatile fashion under the control of GHRH, Ghrelin, and somatostatin and, via a complex signal transduction cascade, initiates the release of IGF-I within many tissues but predominantly the liver and at the growth plate. IGF-I acts in an autocrine and paracrine manner via the IGF-I receptor to stimulate cell proliferation and longitudinal growth. Activation of the pituitary-gonadal axis during puberty occurs via a complex interaction of factors including kisspeptin, leptin, gonadotrophin releasing hormone, and tachykinin ultimately leading to augmentation of GH secretion, the pubertal growth spurt, and fusion of the growth plates. Many other hormones can affect the GH-IGF-I system or directly affect cell proliferation at the growth plate including thyroid hormone, vitamin D, and corticosteroids.
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PMID:Endocrine control of growth. 2361 26

The effects of neonatal thyroid deficiency or hyperthyroidism on the development of neurones containing certain neuropeptides was examined in the brains of rats killed at two weeks of age. Five brain areas were dissected and extracted for radioimmunoassay measurement of vasoactive intestinal polypeptide (VIP), somatostatin, cholecystokinin octapeptide (CCK), substance P and neurotensin, whilst corresponding immunocytochemical data were obtained from a quantitative morphological analysis of cell bodies in the cingulate cortex. The two methods of analysis did not always agree, but in hypothyroidism both the concentration of VIP and the number of cells containing VIP-like immunoreactivity were significantly decreased in the anterior and posterior cingulate cortex. In contrast to these effects on the late maturing VIP neurones, the earlier developing somatostatin system was relatively unaffected, whilst neuropeptides localized in cortical fibres rather than cell bodies (such as substance P and neurotensin) were found by radioimmunoassay to be elevated. Hyperthyroidism had less marked effects than neonatal thyroidectomy, although the concentration of CCK (but not the number of immunostained cells) was significantly increased in the cingulate cortex. Radioimmunoassay results from three subcortical areas showed a decrease in VIP concentration in the hypothyroid hypothalamus, and in hyperthyroidism significant elevations of VIP in the basal ganglia, somatostatin in the hypothalamus and CCK in the hippocampus. It appears that in the brain areas studied thyroid disorders result in dis-synchronous shifts in the developmental patterns of the different neuropeptides, and that the effects of thyroid hormone on peptides as on other transmitters are critically dependent on the developmental profile of the system in question.
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PMID:Effects of changes in neonatal thyroid status on the development of neuropeptide systems in the rat brain. 2487 27


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