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)

Neuronal hypertrophy occurs in a subpopulation of neurons in the infundibular nucleus of post-menopausal women. The hypertrophied neurons contain NKB, SP and estrogen receptor gene transcripts. Although associated with reproductive aging, post-menopausal neuronal hypertrophy is not a sign of central nervous system degeneration. Quite the opposite, because the hypertrophy is accompanied by marked increases in tachykinin gene expression, reflecting increased neuronal activity. We have proposed that infundibular neurons containing NKB, SP and estrogen receptor mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback on gonadotropin release in the human. In addition, there is evidence to suggest that the hypertrophied tachykinin neurons may be involved in the initiation of menopausal flushes. Because menopause affects a well characterized system, and has consistent and substantial changes in hormone levels, we have had the rare opportunity to correlate changes in hormone secretion with structural and neurochemical changes in the human hypothalamus. We suspect that future studies of the hypothalami of post-menopausal women will continue to be a fruitful avenue for investigating neuroendocrine regulation in the human.
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PMID:Hormonal influences on morphology and neuropeptide gene expression in the infundibular nucleus of postmenopausal women. 133 3

Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17 beta-estradiol augmented secretion of histamine and serotonin, starting at 1 microM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17 beta-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca2+ originating from an influx of extracellular Ca2+ in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen's inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.
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PMID:Estradiol augments while tamoxifen inhibits rat mast cell secretion. 138 69

Effects of gonadal steroids on numbers of neurons containing estrogen receptor (ER) and/or substance P (SP) were examined in the anteroventral periventricular nucleus (AVPV) of female and male rats by double-labeling immunohistochemistry employing antibodies specific for ER and SP. Animals were gonadectomized and received subcutaneously either oil alone (Control group), sequential injections of estradiol benzoate and oil (EB + Oil group), or those of EB and progesterone (EB + P group). In the female control rat, a large population of ER-immunoreactive (IR) cells were found clustered throughout the AVPV. They were counted more than 2,000 in total of 4 sections in this nucleus. On the contrary, SP-IR neurons were scarcely observed in the same area of this group. Administration of estrogen to female animals decreased the total number of ER-IR cells to 67% of the control group. In contrast to the supressive effect of estrogen to its own receptor, it induced SP-IR neurons in the AVPV of the female. Approximately 50-80 SP-IR neurons were counted in the 4 sections, and 59% of these neurons expressed ER-IR material in their nuclei. In the female EB + P group, the number of ER-IR neurons also decreased to 79% of the control group. Although the number of SP-IR neurons in this group decreased to 32% of that in the EB + Oil group, a ratio of coexistence of ER-IR material in these neurons increased to 75%. The male control group contained a smaller population of ER-IR cells relative to the female control (1497 vs 2143).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of substance P-immunoreactivity by estrogen in neurons containing estrogen receptors in the anterovental periventricular nucleus of female but not male rats. 753 52

Substance P (SP) and estrogen receptor immunoreactivity overlap in the midbrain central gray (MCG) of female guinea pigs. Estrogen-receptor-containing cells are found throughout the rostrocaudal extent of the MCG. Moderately dense SP immunostaining is also found in this region. SP-immunoreactive punctate structures suggestive of boutons were found in close association with the processes of some estrogen-receptor-immunoreactive neurons. These associations were observed primarily in the lateral and ventrolateral MCG at the midcollicular and caudal levels. This findings suggests an anatomical substrate for interactions between SP and estradiol-sensitive neurons in the midbrain. Such interactions may underlie the effects of SP on female sexual behavior.
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PMID:Convergence of substance P and estrogen receptor immunoreactivity in the midbrain central gray of female guinea pigs. 925 16

Previously, we have observed that the expression of the neuropeptides bombesin (BN-), the mammalian counterpart being gastrin-releasing peptide (GRP), and substance P (SP) in intact normal tissues, such as salivary and laryngeal glands, increases in response to irradiation. In the present study, the aim was to evaluate whether irradiation can have effects on individual cells that normally synthesize neuropeptides. In addition, since these neuropeptides are potentially mitogenic, we studied tumor cells. Therefore, the estrogen receptor-negative human breast cancer cell line MDA-MB-231 and its subline, with acquired doxorubicin resistance, MDA-MB-231 Dox were examined before irradiation and 4, 10, and 15 days after irradiation with 4 Gy (195 kV, 2 Gy fractions with 4 hours interval). Potential dose related changes were studied by delivering single doses of 2 or 9 Gy with the same technique. Immunohistochemical and radioimmunoassay (RIA) methods were used for detection of the SP and BN/GRP. Before, and at all time points following irradiation, a subpopulation in both cell lines displayed an intense immunostaining of SP and BN/GRP. A partial reorganization of the immunoreactive material was observed 10 days after irradiation. The RIA-analyses displayed signs of a dose-related increase, and a time-dependent transient and significant increase in the content of both peptides. The pattern of changes differed between the two peptides, and was especially pronounced in the doxorubicin resistant cells with regard to SP. Another neuropeptide, calcitonin gene related peptide (CGRP), was not detected in the cells used. The results suggest that irradiation has effects on a population of cultured neuropeptide-synthesizing cells. The occurrence and the specific changes obtained in the levels of neuropeptides, in response to irradiation, might imply an importance in the growth of breast cancer cells and in explaining repair processes following irradiation.
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PMID:Enhanced expression of neuropeptides in human breast cancer cell lines following irradiation. 949 54

Estrogen status has profound effects on cutaneous sensitivity in adult female rats. The presence of alpha-estrogen receptor mRNA and protein in NGF-dependent, adult female rat dorsal root ganglion (DRG) neurons raises the possibility that estrogen modulates cutaneous sensation by acting directly on primary afferent neurons, perhaps by altering their sensitivity to NGF. The present study examined the effect of long-term (90 days) daily injections of an estrogen preparation, Premarin (Wyeth-Ayerst, Radnor, PA), to ovariectomized adult rats on lumbar DRG high-affinity NGF receptor, trkA, mRNA levels, and on beta-preprotachykinin (beta-PPT) mRNA levels, which have been shown to be regulated by NGF. Two doses were used in the experiments, the higher dose being 10 times that of the lower dose. Such injections had an effect opposite that reported for short-term, acute estrogen treatment on DRG trkA mRNA levels. The current data show that long-term daily estrogen treatment decreases trkA mRNA levels by 36%. After 90 days of estrogen treatment, no dose effect was evident. Moreover, as would be expected if beta-PPT gene expression is regulated by NGF through the trkA receptor, long-term estrogen treatment decreased DRG neuronal beta-PPT mRNA levels by about 30%. As with trkA, there was no dose effect evident after 90 days of estrogen treatment. These data suggest the possibility that estrogen modulates DRG neuropeptide gene expression and, perhaps, cutaneous sensitivity by regulating NGF receptor gene expression.
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PMID:Long-term estrogen replacement coordinately decreases trkA and beta-PPT mRNA levels in dorsal root ganglion neurons. 1007 1

Women have a higher incidence of inflammatory disorders than men and also appear to perceive painful stimuli differently. It has been suggested that neuroinflammation plays a role in painful bladder disorders of uncertain etiology, such as interstitial cystitis. Nerve growth factor (NGF) is a neurotrophin produced in peripheral tissues that can also mediate pain and inflammation. We found that treatment of mice with the estrogen antagonist ICI 182,780 had no effect on bladder NGF content but decreased bladder NGF messenger RNA. Using immunohistochemistry, we demonstrated that the mucosa is the primary source of NGF in the mouse bladder, and the bladder mucosa also expresses estrogen receptor (ER)-alpha, ER-beta, and the high-affinity NGF receptor tyrosine kinase A. Estrogen may also modulate neurogenic inflammation by interaction with other substances and cells that participate in the pathogenesis of neurogenic inflammation, including substance P, bradykinin, and mast cells. Collectively, these observations indicate that estrogen has the capacity to influence the onset and course of neurogenic inflammation of the bladder.
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PMID:Estrogen and neuroinflammation. 1137 49

Estrogen receptor immunoreactivity and mRNAs are present in spinal cord neurons in locations that are associated with sensory and autonomic innervation of female reproductive organs. The present study was undertaken to examine the expression of estrogen receptor-alpha in the spinal cord during different stages of pregnancy and to determine whether estrogen receptor-alpha-expressing neurons are related to uterine afferent nerves bringing information to the spinal cord at parturition. Immunohistochemistry showed estrogen receptor-alpha-immunoreactive neurons in the dorsal one-half of the spinal cord, i.e., dorsal horn, dorsal intermediate gray areas (dorsal commissural nucleus), and around the central canal and sacral parasympathetic autonomic nucleus of the lumbosacral spinal cord. Neurons in these areas corresponded topographically to the distribution of central processes of visceral primary afferent neurons (e.g., containing calcitonin gene-related peptide and substance P) that innervate and activate second-order spinal cord neurons (evidenced by their expression of Fos) at parturition. Western blots showed that estrogen receptor-alpha increases in the spinal cord, with a peak at day 20 of gestation, followed by a slight decrease by 2 days postpartum. These studies show that estrogen receptor-alpha is expressed by neurons in autonomic and sensory areas of the lumbosacral spinal cord that have connections with the female reproductive system and that the level of estrogen receptor-alpha changes over the course of pregnancy, which may follow profiles of steroid hormones. Many of these neurons may be involved in processing information related to reproductive organ function, changes during pregnancy, and relays to other CNS centers.
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PMID:Estrogen receptor-alpha and neural circuits to the spinal cord during pregnancy. 1244 3

We have investigated whether bladder afferent neurons are likely to be targets for circulating estrogens by mapping estrogen receptor (ER) distribution in lumbosacral dorsal root ganglia (DRG) of adult female rats. Sensory neurons innervating either the detrusor or trigone regions were identified by application of fluorescent retrograde tracer dyes to the bladder wall. Labelled neurons were classified by their immunoreactivity for either type of ER (ERalpha or ERbeta) and further compared with subpopulations of neurons containing substance P, calcitonin gene-related peptide and vanilloid receptor (a marker of polymodal nociceptors). Both ER types were expressed in numerous sensory neurons of either upper lumbar (L1/L2) or lower lumbar/sacral (L6/S1) ganglia and there was almost complete coexpression of ERalpha and ERbeta. ER-positive neurons were mainly small-medium size (18-25-microm diameter), indicating that they may be nociceptors and/or supply visceral targets. Most bladder-projecting neurons expressed ERs and the majority of these also expressed neuropeptides or vanilloid receptor. Afferent neurons supplying detrusor and trigone regions had similar immunohistochemical features. About a third of the bladder-projecting neurons expressed both ER and vanilloid receptor, suggesting a mechanism by which estrogens could influence bladder pain. The prevalence of different chemical classes of ER-positive bladder-projecting neurons was reflected throughout the entire population of neurons in dorsal root ganglia of these spinal levels, suggesting that neurons supplying other pelvic visceral targets may have similar chemical profiles. These results suggest that many functional classes of sensory neurons innervating the lower urinary tract are likely to be targets for circulating estrogens, including many nociceptor neurons. The coexistence of ERalpha and ERbeta suggests a broad range of potential mechanisms by which estrogens may exert their genomic effects in this system.
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PMID:Estrogen receptor expression in lumbosacral dorsal root ganglion cells innervating the female rat urinary bladder. 1279 5

Prior to parturition the non-pliable uterine cervix undergoes a ripening process ("softens" and dilates) to allow a timely passage of the fetus at term. The exact mechanism(s) triggering and involved in cervical ripening are unknown, though evidence for a role for sensory neurons and their contained neuropeptides is emerging. Moreover, an apparent increase in neuropeptide immunoreactive nerves occurs in the cervix during pregnancy, maternal serum estrogen levels rise at term and uterine cervix-related L6-S1 dorsal root ganglia (DRG) sensory neurons express estrogen receptor (ER) and neuropeptides. Thus, we sought to test the hypothesis that the neuropeptide substance P (SP) changes biosynthesis and release over pregnancy, that estrogen, acting via the ER pathway, increases synthesis of SP in DRG, and that SP is utilized in cervical ripening at late pregnancy. Using immunohistochemistry, in situ hybridization, reverse transcriptase-polymerase chain reaction (RT-PCR) and radioimmunoassay (RIA), we investigated coexpression of ER-alpha/beta and SP; differential expression of ER-alpha and -beta mRNA in DRG neurons; SP synthesis in DRG; and changes in SP concentration in the cervix, DRG and spinal cord over pregnancy. In addition, the effect of exogenous estrogen on SP synthesis in L6-S1 DRG of ovariectomized rats was examined. SP-immunoreactive neurons expressed ER-alpha and ER-beta. SP synthesis (expressed as beta-PPT mRNA label) was prominent in small DRG neurons. SP concentration increased in the L6-S1 DRG and spinal cord segments, with a peak at Day 20 of gestation, but decreased in the cervix during the first two trimesters, with a rise over the last trimester to Day 10 levels. SP and ER-alpha mRNA synthesis increased in DRG over pregnancy but ER-beta mRNA levels were largely unchanged. When ovariectomized rats were treated with exogenous estrogen, SP mRNA synthesis in the DRG increased in a dose-related manner, an effect blocked by ER blocker ICI 182 780. From these results, we postulate that synthesis of SP in L6-S1 DRG and utilization in the cervix increase over pregnancy and this synthesis is under influence of the estrogen-ER system, most likely ER-alpha. We postulate that SP may play a role in cervical ripening and, consequently in the birth process.
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PMID:Substance P in the uterine cervix, dorsal root ganglia and spinal cord during pregnancy and the effect of estrogen on SP synthesis. 1289 64


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