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)

Experiments were designed to identify the neural cell type(s) responsible for the aromatization and 5 alpha-reduction of androgens in the rat hypothalamus. Primary cultures of fetal rat hypothalamic cells, which had enhanced neuronal morphology, were treated at various times after plating with kainic acid (KA), a neurotoxic agent which selectively destroys neuronal cells. Neuronal morphology was disrupted in a time (0-6 days)- and dose (10(-4)-10(-2) M)-dependent fashion after KA treatment, with no apparent change in the appearance of the flattened, underlying non-neuronal cells. KA treatment for 4 days decreased aromatization by 94% in a dose-dependent fashion (10(-4)-10(-2) M KA), while 5 alpha-reduction declined by no more than 25%. A 6-day time course with 10(-3) M KA showed a dramatic decline in aromatization and no alteration in 5 alpha-reduction. In control experiments, substance P, a neuronal peptide, declined after KA treatment while the activity of glutamine synthetase, a glial enzyme, did not change. We conclude from these results that aromatase is localized primarily to neuronal cells in the hypothalamus while 5 alpha-reductase is confined primarily to non-neuronal cells.
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PMID:Localization of aromatase and 5 alpha-reductase to neuronal and non-neuronal cells in the fetal rat hypothalamus. 242 95

Experiments were conducted to study the regulation of the developmental pattern of aromatase in the forebrain of the perinatal rat. Two experimental designs were used: aromatase measured in primary cultures of fetal hypothalamic cells and in cell-free preparations of forebrain tissue excised at varying ages. In cultured cells, aromatase decreased logarithmically at a slow rate (t1/2 = 7.8 days). Norepinephrine caused a pronounced dose (4 x 10(-6) M) and time-dependent (2-6 days) drop in aromatase without affecting the levels of 5 alpha-reductase or substance P. In isolated tissue, aromatase activity was compared with the concentrations of norepinephrine and dopamine in the forebrain of males vs females at different perinatal ages and in discrete forebrain areas at postnatal day 4. In no case was a sex difference in catecholamines seen. An overall developmental decline in aromatase was associated with developmental increases in catecholamine levels. Acute treatment with the beta-agonist, isoproterenol, had no effect on brain aromatase activity.
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PMID:Studies on the role of catecholamines in the regulation of the developmental pattern of hypothalamic aromatase. 350 14

Corpora lutea of all species investigated so far, including the human, produce oxytocin and a variety of other regulatory peptides. The role of these peptides is largely unknown. The subtypes of large luteal cells are able to produce tumour necrosis factor (TNF) and at the end of the luteal phase TNF-producing macrophages invade the aged corpus luteum, indicating that this cytokine may be involved in the process of luteolysis. The present contribution reviews briefly the known functions of oxytocin and substance P in the corpus luteum and then elaborates the possible involvement of luteal and macrophage TNF during luteolysis. Oxytocin applied to intact corpus luteum stimulates the secretion of progesterone and oestradiol. The stimulation of progesterone secretion by oxytocin is due to the stimulated oestrogen production. TNF, when tested in vitro, inhibits both luteal cell progesterone and oestradiol production. The TNF-mediated inhibition of aromatase activity therefore prevents the luteotrophic effects of a variety of peptides including oxytocin. This appears to be the mechanism by which TNF induces luteolysis.
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PMID:Luteotrophic and luteolytic actions of ovarian peptides. 750 69

The release of PGF2 alpha and PGE2, progesterone, androgens and oestradiol in vitro, and the aromatase activity in the brain of the male lizard Podarcis sicula sicula during three different phases of the reproductive period were evaluated. In addition, the effects of salmon GnRH, substance P, salmon GnRH antagonist, substance P antagonist, PGF2 alpha, PGE2 and acetylsalicylic acid on the release of prostaglandins and sex steroids and on aromatase activity in the brain were evaluated during the same three phases. PGF2 alpha, oestradiol and aromatase activity were higher during the refractory phase, androgens during the fighting phase, and progesterone during the mating phase, while PGE2 was lower during the refractory phase. Treatment with salmon GnRH increased PGF2 alpha, oestradiol and aromatase activity, but decreased the amount of androgens released. Substance P decreased PGF2 alpha, oestradiol and aromatase activity, but increased the amount of androgens released. PGF2 alpha increased oestradiol and aromatase activity, but decreased the amount of androgens released. Acetylsalicylic acid decreased PGF2 alpha, oestradiol and aromatase activity, but increased the amount of androgens released. These data suggest that salmon GnRH and substance P have different roles in reproductive processes, with opposite mechanisms, in the central nervous system of this male lizard: salmon GnRH seems to be involved in regulating the refractory phase, while substance P plays a role in regulating the fighting phase.
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PMID:Relationships among GnRH, substance P, prostaglandins, sex steroids and aromatase activity in the brain of the male lizard Podarcis sicula sicula during reproduction. 752 52

In the present study we investigated the effects of various tachykinins on the secretory activity of rat Sertoli cells in vitro. Sertoli cells were isolated from testes of immature Sprague Dawley rats, cultured for 4 days and thereafter incubated with three concentrations (0.1 pM, 1 pM or 100 pM) of substance P (SP), neurokinin A (NKA), neuropeptide K (NPK) or neuropeptide gamma (NPG) for 24 h. Levels of transferrin and lactic acid were determined in the culture media and expressed per micrograms of cellular DNA. Among all the peptides studied, NPG exhibited the greatest stimulatory effect on the release of transferrin and lactate, with NKA and NPK being less potent and SP being the least potent. Also, the effects of tachykinins on the aromatase activity of cultured Sertoli cells, as reflected by their ability to metabolize testosterone to estradiol (E2), were studied. No stimulatory effect was observed at lower concentrations (1 pM), while at 100 pM both NPG and NKA increased estradiol levels in the medium. SP and NPK had no significant effect on estradiol levels in the medium. This study reveals that tachykinins are able to influence the secretory activity of Sertoli cells, and that some of these peptides can also enhance the aromatase activity. Thus there is a possibility that tachykinins may have a physiological role as modulators of the function of Sertoli cells.
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PMID:Effects of tachykinins on the secretory activity of rat Sertoli cells in vitro. 786 86

Aromatase in the diencephalic neurons, the level of which increases transiently during the prenatal to neonatal period, has been suggested to be involved in control of sexual behavior and differentiation of the CNS. Effects of neurotransmitters on levels of aromatase mRNA in cultured neurons were investigated to determine factors regulating the developmental increase that occurs in level of fetal brain aromatase. The expression of aromatase in diencephalic neurons of fetal mice at embryonic day 13, cultured in vitro, was significantly affected by alpha 1-adrenergic receptor ligands. Aromatase mRNA levels were higher in neurons treated with the alpha 1-agonist phenylephrine than in control neurons, whereas prazosin, an alpha 1-antagonist, suppressed this increase, and ligands for alpha 2- or beta-adrenergic receptors did not exert any influence. The profile of alpha 1-adrenergic receptor subtypes during actual development in vivo suggested that the alpha 1B subtype is in fact responsible for the signal transduction. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide also increased the level of expression along with phorbol 12-myristate 13-acetate and dibutyrylcyclic GMP, whereas forskolin and dibutyryl-cyclic AMP caused a decrease. These data indicate that stimulation via alpha 1 (possibly alpha 1B)-adrenergic receptors, as well as receptors of specific neuropeptides, controls the expression of aromatase in embryonic day 13 diencephalic neurons through activation of protein kinase C or G. beta-Adrenergic receptors would not appear to participate in the regulation, judging from their developmental profile, although cyclic AMP might be a suppressive second messenger.
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PMID:Neurotransmitter-mediated regulation of brain aromatase: protein kinase C- and G-dependent induction. 886 18

A transient increase in aromatase activity is known to occur in the hypothalamus of rodents in pre- and postnatal periods. The mechanisms regulating such a developmental increase of brain aromatase was studied in fetal mouse diencephalic cells, by measuring aromatase mRNA levels by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. When slices of diencephalon were cultured on embryonic day (E) 12, E13 and E15, the level of aromatase mRNA continued to increase for the first 2 to 3 days. A time-dependent increase of mRNA was also shown for 3 days in E13 neuronal cells dissociated with papain and cultured in chemically defined medium. However, no significant increase was observed in E10 or E11 brain cells cultured by either method. Aromatase mRNA was detected in neither cerebral cortex neurons nor astrocytes. An alpha1-selective adrenergic agonist, phenylephrine, increased aromatase in the E13 diencephalic neurons in culture, whereas prazosin, an alpha1-antagonist, suppressed the mRNA level. Ligands for alpha2- or beta-adrenergic receptors did not alter the mRNA level. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide as well as phorbol 12-myristate 13-acetate and dibutyryl-cyclic GMP all increased the mRNA level. We concluded that: (a) the developmental increase of aromatase mRNA in diencephalic neurons is an autonomous event and is perhaps genetically regulated after E12; (b) aromatase mRNA is expressed in a cell type- and region-specific manner; and (c) protein kinases C and G activated via receptors of the specific neurotransmitters may be involved in modulation of the developmental expression of aromatase mRNA.
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PMID:Autonomous expression of aromatase during development of mouse brain is modulated by neurotransmitters. 936 5

Tachykinins are vasoactive and smooth muscle-contracting peptides with widespread localizations. Tachykinins have been localized in the nerve fibres that supply the testes, in the Leydig cells of different animal species, and also in Sertoli cells of the Siberian hamster testes. The presence of substance P (SP) has also been demonstrated in ejaculated human spermatozoa and in the seminal plasma. Tachykinins have been shown to inhibit the release of testosterone by testicular fragments or by isolated Leydig cells in vitro. Acting on Sertoli cells, tachykinins have been shown to stimulate the release of lactate and transferrin by these cells in vitro, and also to stimulate aromatase activity. Leydig and Sertoli cells express the Preprotachykinin A gene, and this fact strongly suggests that tachykinins can be synthesized in the testes. These findings suggest that tachykinins may have a physiological function in the testes as modulators of the functions of the different cell types contained in these organs.
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PMID:Tachykinins and their possible modulatory role on testicular function: a review. 1284 95

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in this area and the control of spinal aromatase activity is thought to play an important role in the estrogenic control of nociception. The coexistence of aromatase and nociceptive terminals suggests a role for aromatase cells in pain-related processes, but whether terminals releasing nociceptive neuropeptides (e.g., substance P) actually contact aromatase neurons is unknown and the factors that control spinal aromatase activity have not yet been identified. In the present study we analyzed by double-label immunocytochemistry the distribution in the Japanese quail spinal cord, of aromatase and of substance P or its receptor (neurokinin 1 receptor). All antigens were mainly localized in laminae I and II as observed in mammals. Most aromatase neurons were colocalized with neurokinin 1 receptors and were in close apposition with substance P-immunoreactive fibers. These results suggest that aromatase neurons are responsive to noxious stimulation and may participate in the control of nociception. Furthermore, spinal aromatase activity could be controlled by substance P through a regulation of the aromatase gene transcription as reported for the mouse diencephalon and/or through neurokinin 1 receptor-dependent phosphorylation of the aromatase protein.
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PMID:Specific innervation of aromatase neurons by substance P fibers in the dorsal horn of the spinal cord in quail. 1294 89

Dorsal root ganglia (DRG) which contain glial cells and somas of primary sensory neurons are pivotal for neural transmission between the peripheral and central nervous systems. It is well established that neuropeptides such as substance P and calcitonin gene-related peptide located in DRG neurons control sensory and pain mechanisms. However, contrary to the brain and spinal cord which are extensively investigated, DRG received little attention. Therefore, the current knowledge on DRG may be far to represent their complete neurochemical potential. For instance, until 1997, nothing was known on DRG neurosteroidogenic ability but recently, several investigations have shown that DRG contain various key enzymes synthesizing neuroactive neurosteroids. To provide new advances into DRG neurochemistry, we reviewed and highlighted herein basic and functional evidence showing that neurosteroids are produced in DRG through a neuron-glia crosstalk mechanism. Indeed, key enzymes producing neurosteroids including pregnenolone, progesterone, dihydroprogesterone and estradiol are differentially expressed in DRG cell types. Cytochrome P450side-chain-cleavage is located in DRG neurons and satellite glial cells, 3beta-hydroxysteroid dehydrogenase is expressed in Schwann cells and neurons, 5alpha-reductase is localized in satellite glial and Schwann cells (not in neurons) while aromatase is present in neurons but not in glia. Recent studies also revealed that DRG neurosteroidogenesis is a physiologically relevant process selectively regulated under pathological conditions. Acting through paracrine and autocrine mechanisms, endogenous neurosteroids modulate DRG sensory functions and protect DRG neurons against death. The paper suggests that DRG neurosteroidogenic components may be targeted for the development of therapies against peripheral nerve injury-induced afferent noxious stimulations.
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PMID:Progress in dorsal root ganglion neurosteroidogenic activity: basic evidence and pathophysiological correlation. 2043 98


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