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)

Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotransmitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypothalamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.
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PMID:Transmitter content and afferent connections of estrogen-sensitive progestin receptor-containing neurons in the primate hypothalamus. 135 61

Substance P (SP) immunoreactivity is detectable in the rat pituitary by RIA; however, immunolocalization has been difficult. We used a sensitive immunogold silver-enhancement staining technique to cytochemically locate SP in the gland. SP-immunoreactive (SP-ir) cells were seen in anterior pituitary (AP), and occasional SP-ir fibers and terminals were seen in both AP and posterior pituitary. Colocalization studies showed the vast majority of SP-ir cells in the male AP to be also immunoreactive for growth hormone (GH). These GH/SP-ir cells represent approximately 23% of the somatotroph population in the male. SP-ir cells did not colocalize with lactotrophs, gonadotrophs, or corticotrophs; however, rare thyroid-stimulating hormone/SP-ir cells were found in the male AP. Comparisons of pituitaries from males and females revealed that females have 70% fewer SP-ir cells and that only approximately 6% of the somatotrophs in the female express SP. This sexual dimorphism is diminished in 6-day ovariectomized rats because this treatment increases the GH/SP-ir cell population 3-fold. This result suggests that the previously reported estrogen-induced decrease in SP gene and peptide expression in the pituitary occurs, at least in part, in a subpopulation of somatotrophs. To test this hypothesis, distribution of SP-ir cells was examined in pituitaries from estrogen- and oil-treated ovariectomized rats. Estrogen reduced the percentage of somatotrophs with SP immunoreactivity by 70% compared with ovariectomized oil-treated controls, indicating that estrogen most likely regulates SP levels in the pituitary by acting on a subpopulation of somatotrophs to suppress SP expression. Estrogen does not appear to alter SP immunoreactivity that is detected in the additional population of SP cells that colocalize with thyroid-stimulating hormone. These SP-expressing thyrotrophs were seen 6-fold more frequently in the female than in the male pituitary, regardless of steroid status. These studies reveal that males have more total SP-ir cells in the AP than do females and that there is a sexually dimorphic pattern of SP distribution in the gland. Males have a higher percentage of SP-ir GH cells, whereas females have more SP-ir thyrotrophs than do males. Identification of independently regulated SP-ir somatotroph and thyrotroph populations provides a basis for investigating the roles of SP in autocrine or paracrine regulation of pituitary hormone secretion.
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PMID:Sexually dimorphic distribution of substance P in specific anterior pituitary cell populations. 170 31

Estrogen-induced increases in uterine blood flow appear to require de novo protein or polypeptide synthesis. In the present experiments a chronically catheterized nonpregnant sheep preparation was used to determine the uterine vascular effects of vasoactive intestinal polypeptide (VIP), neurotensin, and substance P. These effects were compared to those of bradykinin and the most potent vasodilator prostaglandin, prostacyclin. An intra-arterial catheter was placed in a branch of the main uterine artery to allow administration of the compounds directly into the uterine vasculature. Uterine blood flow was continuously monitored via an electromagnetic flow transducer on the maine uterine arteries. VIP, bradykinin, and prostacyclin were equally potent as vasodilators of the uterine vasculature, while neurotensin and substance P were totally devoid of vasoactivity. Unlike estradiol, bradykinin and VIP produced significant changes in systemic arterial pressure and heart rate, suggesting that these compounds may not have responsible for mediating the uterine vascular response observed after estrogen. However, VIP was a potent uterine vasodilator and was able to totally ablate uterine contractile activity, suggesting that this endogenously occurring polypeptide may be important in regulating uterine hemodynamics and contractile activity.
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PMID:Effects of vasoactive polypeptides on the uterine vasculature. 616 38

In the rat, reproduction and sexual behavior are controlled by the gonadal steroid regulation of synaptic interactions within the sexually dimorphic limbic-hypothalamic system. The effects of estrogen on the ventromedial nucleus of the hypothalamus, one nucleus within the circuit, are central to the modulation of this behavior. Involvement of the neuropeptide substance P, a member of the tachykinin family of neuropeptides, has been implicated in the regulation of both lordosis behavior and gonadotropin release. However, previous studies have provided conflicting evidence as to whether levels of substance P in the ventromedial nucleus of the hypothalamus are modulated by circulating estrogens. To study this question further, in situ hybridization histochemistry was used to examine levels of beta-preprotachykinin mRNA, which encodes substance P and other tachykinins, in the ventrolateral subdivision of the ventromedial hypothalamus at 10 consecutive timepoints over a 4 day period subsequent to an acute administration of estrogen. Following estrogen treatment, beta-preprotachykinin mRNA expression was increased in cells of the ventrolateral portion of the ventromedial nucleus of the hypothalamus which constitutively express beta-preprotachykinin mRNA; however, there were no statistically significant changes in the number of cells that express detectable levels of beta-preprotachykinin mRNA in the ventrolateral portion of the ventromedial nucleus. Estrogen treatment produced two peaks of beta-preprotachykinin mRNA expression, the first at 2 h and the second at 48 h after the injection of estrogen. These data indicate that estrogen has both rapid and prolonged effects on beta-preprotachykinin mRNA levels, suggesting that estrogen may affect different cellular mechanisms relevant to the induction of beta-preprotachykinin mRNA expression.
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PMID:Temporal regulation by estrogen of beta-preprotachykinin mRNA expression in the rat ventromedial nucleus of the hypothalamus. 770 79

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

Cholecystokinin, substance P and methionine enkephalin all regulate the display of reproductive behaviour. Their expression is exquisitely regulated by estrogen in the limbic-hypothalamic circuit, a circuit that regulates the display of estrogen-sensitive female reproductive behavior. Relatively little is known, however, about the interaction of endogenous opioid peptides with cholecystokinin and substance P in the limbic-hypothalamic circuit. Opiates antagonize the release of cholecystokinin and substance P in the hypothalamus and periaqueductal gray and stimulate cholecystokinin messenger RNA levels in the amygdala. To determine the effect of endogenous opioid input on estrogen-induced cholecystokinin, enkephalin and substance P expression, in situ hybridization histochemistry was used to examine estrogen-induced messenger RNA levels of these neuropeptides in specific nuclei of the limbic system and hypothalamus in the presence of opiate receptor antagonists. Estrogen treatment of ovariectomized rats significantly elevated cholecystokinin messenger RNA levels in the central portion of the medial preoptic nucleus, the encapsulated portion of the bed nucleus of the stria terminalis and the posterodorsal medial amygdala, as well as increased preproenkephalin and preprotachykinin messenger RNA levels in the ventromedial hypothalamic nucleus and the posterodorsal medial amygdala. The universal opiate receptor antagonist naltrexone and the delta-opiate receptor antagonist naltrindole each potentiated the estrogen-induced increase and elevated cholecystokinin messenger RNA levels an additional 1.9- to 2.8-fold depending on the nucleus examined, but had no effect on the estrogen-induced expression of either preproenkephalin or preprotachykinin messenger RNA. beta-Funaltrexamine, a mu-opiate receptor antagonist, had no effect on the medial preoptic or medial amygdaloid cholecystokinin messenger RNA levels or on the estrogen-induced expression of preproenkephalin messenger RNA but did cause a decrease in estrogen-induced cholecystokinin messenger RNA levels in the bed nucleus of the stria terminalis and a decrease in the preprotachykinin messenger RNA levels in the ventromedial hypothalamic nucleus. These results indicate that endogenous opioids, acting on the delta-opiate receptor within nuclei of the limbic-hypothalamic circuit, restrain the estrogen-induced increase of cholecystokinin messenger RNA expression. Activation of the mu-opiate receptor, however, may facilitate cholecystokinin messenger RNA expression in the bed nucleus of the stria terminalis and preprotachykinin messenger RNA expression in the ventromedial hypothalamic nucleus. Thus, endogenous opioid peptides may act in a site- and receptor-specific manner to modulate estrogen-induced neuropeptide levels in the limbic system and hypothalamus.
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PMID:Opiate receptors modulate estrogen-induced cholecystokinin and tachykinin but not enkephalin messenger RNA levels in the limbic system and hypothalamus. 928 50

Estrogen is known to improve in the short term the impaired endothelium-dependent vasodilating responses in postmenopausal women, which may account in part for the beneficial cardiovascular effects of the female hormone. Endothelium-dependent vasodilation is achieved by combined effects of endothelium-derived prostacyclin, nitric oxide (NO), and hyperpolarizing factor. In this study, we investigated our hypothesis that short-term estrogen improves both NO-mediated and non-NO-mediated endothelium-dependent vasodilation in postmenopausal women. The study included 12 postmenopausal women (aged 64 +/- 3 years). The forearm blood flow was measured by strain-gauge plethysmography. The forearm vascular responses to the endothelium-dependent vasodilators, acetylcholine and substance P, were examined before and after intravenous administration of conjugated estrogen and subsequently after intraarterial infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis. Short-term estrogen augmented the forearm vasodilating responses to both acetylcholine and substance P. The treatment with L-NMMA almost abolished the augmented response to acetylcholine but did not affect that to substance P. The forearm vascular response to sodium nitroprusside was unchanged by the estrogen administration. These results indicate that estrogen augments (in the short-term) both NO-mediated and non-NO-mediated endothelium-dependent forearm vasodilation in postmenopausal women. Thus the beneficial effect of estrogen on endothelial vasodilator function appears to extend to non-NO-dependent mechanism(s).
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PMID:Short-term estrogen augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilation in postmenopausal women. 933 8

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

In the guinea pig, steroid target cells reside in the ventrolateral hypothalamic nucleus (VLH), an important site in the mediation of female receptive behavior, and in the arcuate nucleus (AR), a structure essential for stimulation effects of ovarian hormones on gonadotropin secretion. However, the mechanisms by which these steroid-dependent reproductive neuroendocrine processes occur are only partially understood. Estrogen is known to affect the hypothalamus content of certain neuropeptides. In the present study, we investigated the effects of estradiol benzoate (EB) on immunoreactivity of neurons containing one of three following neuropeptides: somatostatin (SOM), neurotensin (NT) and substance P (SP) in VLH and AR. The number of immunoreactive (IR)-neurons was quantified in anatomically matched sections through VLH and AR of ovariectomized (OVX), OVX + EB and OVX + oil-treated guinea pigs. Analysis of variance revealed that the number of SOM-IR and SP-IR neurons significantly increased in all regions of VLH of OVX + EB-treated guinea pigs as compared to OVX or OVX + oil-treated animals (P < 0.01) but showed no EB effect on the number of NT-IR neurons. Although the number of SOM-IR and NT-IR neurons slightly increased following treatment with EB in AR, analysis of variance revealed no significant change. The present results provide additional information relevant to possible involvement of these neuropeptides in facilitation of female typical sexual behavior.
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PMID:Estrogen modulation of neuropeptides: somatostatin, neurotensin and substance P, in the ventrolateral and arcuate nuclei of the female guinea pig. 1021 66

A population of adult dorsal root ganglion (DRG) neurons bind NGF with high affinity and express the trkA gene. In these cells, NGF regulates gene expression and function. Recently, a number of laboratories reported the presence of estrogen receptors in DRG neurons and profound effects of estrogen on DRG gene expression. Our laboratory, for example, has reported a significant and coordinate decrease in DRG trkA and beta-preprotachykinin (beta-PPT) mRNA levels following 90 days of daily estrogen injections to ovariectomized (OVX) rats. These data suggest, as has been suggested for medial septal cholinergic neurons, that estrogen may collaborate with NGF in the regulation of DRG neuronal gene expression and function. The current study examined further this potential collaboration in the DRG by determining the effect of short-term estrogen replacement in OVX rats on DRG trkA mRNA levels following sciatic nerve transection and the resulting removal of a vital source of NGF for those cells. In OVX rats, about 40% of lumbar DRG neurons contained trkA mRNA. Short-term estrogen replacement had no effect on the percentage of neurons containing trkA mRNA, but increased the mean trkA mRNA level in uninjured DRGs of OVX rats by 23%. Axotomy in OVX rats reduced the mean trkA mRNA level by 55% but did not significantly decrease the percentage of neurons containing the mRNA. Estrogen replacement, 7 days after axotomy, partially and significantly restored the mean trkA mRNA level. It was 49% greater than that of the untreated axotomized DRGs. It did not, however, significantly increase the percentage of DRG neurons containing trkA in axotomized DRGs. These observations show that short-term estrogen has an opposite effect on DRG neuronal trkA mRNA levels as compared to that of long-term estrogen demonstrated in our previous study. Moreover, the current data show that estrogen regulates trkA mRNA levels in the absence of target-derived NGF. These data suggest that estrogen may collaborate with NGF in the maintenance of normal adult DRG gene expression and function. Furthermore, these data suggest that loss of estrogen, such as that associated with menopause, may contribute to a decline in DRG neuronal function and an exacerbation of ongoing neuropathic processes.
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PMID:Effects of short-term estrogen replacement on trkA mRNA levels in axotomized dorsal root ganglion neurons. 1050 14


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