Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the vasodilator calcitonin gene-related peptide (CGRP) is increased in pulmonary neuroendocrine cells in response to hypoxia. To quantify the change, we have now examined lung of adult male Wistar rats exposed to hypoxia (FIO2 = 0.1) for 1 wk and littermate controls. Sections of lung were immunostained simultaneously using rabbit antiserum to rat alpha-CGRP with the peroxidase antiperoxidase technique. The area and integrated optical density of each group of endocrine cells were measured using an image analyzer. For each animal, the summed integrated optical density of endocrine cells divided by the sum of their areas was used as a measure of CGRP-like immunoreactivity. The intensity of immunostaining of endocrine cells in the respiratory portion of the lung was 43% greater than that of endocrine cells along the conducting airways (P less than 0.001). The intensity of staining was increased by approximately 12% (P less than 0.04) after 7 d of hypoxia with no apparent difference in the response of central and peripheral endocrine cells. Measurements of staining intensity of CGRP-coupled agarose beads indicated that a 12% change in staining intensity corresponded to a 15 to 20% change in the concentration of CGRP or CGRP-like immunoreactive material. The supra-optimal dilution technique (measurement of the increase in the number of immunoreactive cells upon sequential immunostaining with a supra-optimal and then an optimal dilution of primary antiserum) detected the increase in CGRP-like immunoreactivity after 7 d of hypoxia with a high degree of statistical significance (P less than 0.005) using the same number of sections.
Am J Respir Cell Mol Biol 1990 Dec
PMID:Quantitative immunocytochemistry shows calcitonin gene-related peptide-like immunoreactivity in lung neuroendocrine cells is increased by chronic hypoxia in the rat. 214 51

Regulation of expression of the human calcitonin gene was found to differ between two tumor lines of different tissue origin, medullary thyroid carcinoma (TT line) and small-cell lung carcinoma (DMS53 line). Distal 5' DNA elements between -750 and -2000 exhibited a stronger basal activity in DMS53 than in TT cells, whereas proximal DNA sequences between -132 and -252 mediated a dramatic cyclic AMP response in TT but not DMS53 cells.
Mol Cell Biol 1990 Apr
PMID:Differential utilization of calcitonin gene regulatory DNA sequences in cultured lines of medullary thyroid carcinoma and small-cell lung carcinoma. 215 43

We found an increase in calcitonin gene-related peptide (CGRP)-like immunoreactivity in motoneurons of rat spinal cord after peripheral axotomy. By means of in situ hybridization histochemistry and Northern blotting, we further demonstrated that this increase was the result of increased levels of alpha-CGRP mRNA, not beta-CGRP mRNA. The increased level of alpha-CGRP mRNA was maintained for at least 5 weeks, and was present on both sides. In addition, alpha-CGRP and beta-CGRP mRNAs had different distributions from each other in the dorsal root ganglia and levels of both were decreased after axotomy. These results indicate that alpha-CGRP and beta-CGRP are regulated independently and have different roles in the motor and sensory systems of the spinal cord.
Brain Res Mol Brain Res 1990 May
PMID:Alpha-CGRP and beta-CGRP mRNAs are differentially regulated in the rat spinal cord and dorsal root ganglion. 216 5

Motoneurons express calcitonin gene-related peptide (CGRP). Previous studies have shown that CGRP immunoreactivity is regulated by testosterone in the androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In this research the effect of plasma levels of testosterone on the expression of alpha CGRP mRNA in the SNB motoneurons of adult male rats was studied with in situ hybridization. The number of motoneurons expressing alpha CGRP mRNA and the level of alpha CGRP mRNA expression was significantly higher in the SNB of castrated male rats than in the SNB of gonadally intact rats. Using a 5x background labeling criterion in castrated rats 88.1 +/- 4.5% while in intact rats 75.3 +/- 6.4% of SNB motoneurons expressed alpha CGRP mRNA. Testosterone replacement at the time of castration prevented the effect of castration on the expression of alpha CGRP mRNA in SNB motoneurons. In castrated rats, the increase in the number of SNB cells expressing CGRP was the result of increased steady state levels of alpha CGRP mRNA in all SNB neurons.
Brain Res Mol Brain Res 1990 Jul
PMID:Steroid regulation of calcitonin gene-related peptide mRNA expression in motoneurons of the spinal nucleus of the bulbocavernosus. 216 68

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and dexamethasone (DEX) influence synthesis and secretion of various hormones. Recent reports concerning the interaction of the two steroids revealed opposite--agonistic as well as antagonistic--effects in different biological systems. As calcitonin (CT) gene expression is affected by both agents, inhibited by 1,25(OH)2D3 and stimulated by DEX, we utilized CT secretion and storage as a model to study the combined effects of the two hormones. A human C cell carcinoma cell line (TT) was used, incubating the cells for a period of 4 days with 1,25(OH)2D3 and DEX alone and in combination. 1,25(OH)2D3 resulted in a decrease, whereas DEX resulted in a increase of CT secretion and content. Combining the two steroids, 1,25(OH)2D3 surprisingly abolished the stimulation of DEX on CT secretion and content. The underlying mechanism is yet unclear and could be envisioned to include steroid receptor regulation or gene transcription.
Mol Cell Endocrinol 1990 Jul 09
PMID:1,25-Dihydroxyvitamin D3 suppresses dexamethasone effects on calcitonin secretion. 221 27

Estrogen deficiency following natural or surgical menopause, is thought to be the main factor leading to postmenopausal bone loss. Furthermore, after estrogen failure a significant reduction of intestinal calcium absorption and a negativization of calcium balance has been observed. The mechanism of estrogen effect on skeletal tissue is not yet fully elucidated. Recently, specific receptors for estrogens in osteoblastic cells have been described; however their low density does not give a full explanation about their functional role. Therefore estrogens act, at least in part, indirectly through calciotropic hormones. In order to further elucidate this issue, we performed some studies in postmenopausal osteoporotic patients and in fertile oophorectomized women. In the first double blind placebo controlled study, after a 1-year estrogen treatment period we observed an increase in bone mineral content in the hormone-treated patients. Furthermore, in all treated patients an improvement of intestinal calcium absorption was detected, while 1,25-dihydroxy-vitamin D serum levels did not show significant changes. To further analyse the relationship between estrogens (E) and calcitonin (CT) in postmenopausal osteoporosis, we performed a double blind placebo controlled study to evaluate the effects of 1-yr estro-progestative treatment on CT secretory reserve, evaluated by calcium infusion test. Blood levels of CT showed a progressive increase during the study period in the hormone-treated group, with a significant increase in the CT response to calcium stimulation test, suggesting a modulation of CT secretion by E. Recently, we performed two studies in fertile oophorectomized women. In the first, we followed longitudinally 24 fertile women for 1 yr. In these patients we measured, before and after oophorectomy, biochemical indexes of bone metabolism and bone mass. During the observation period a significant increase in bone resorption and a significant drop in intestinal calcium absorption was observed. In the second study, performed on 14 women before and 6 months after oophorectomy, a treatment with conjugated estrogens allowed the correction of the primary intestinal defect responsible for the reduced calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
J Steroid Biochem Mol Biol 1990 Nov 20
PMID:Calcitonin, estrogens and the bone. 225 49

Using indirect immunofluorescence techniques, we have found that calcitonin gene-related peptide-like immunoreactivity is present in the neuromuscular junctions of somatic muscles as well as in almost all motor neurons of the lumbar enlargement of 1-week-old rats. It gradually decreases in both motor neurons and motor nerve endings as the animal grows up and completely disappears from the neuromuscular junctions in adult rats, persisting only in the motor nerve endings on the intrafusal fibers. In situ hybridization experiments have shown that the down-regulation of calcitonin gene-related peptide-like immunoreactivity is strictly related to a reduction in CGRP mRNA levels in the spinal motor neurons. These results indicate that the expression of CGRP is developmentally regulated in spinal cord alpha motor neurons. They also suggest that the peptide may play an important role at the immature neuromuscular junction.
J Mol Neurosci 1990
PMID:Developmentally regulated expression of calcitonin gene-related peptide at mammalian neuromuscular junction. 227 48

The pre-mRNA encoding calcitonin (CT) and CT gene-related peptide (CGRP) is differentially processed in a tissue-specific fashion to include exon 4 (which encodes CT) or exclude this exon and splice to exon 5 (which encodes CGRP). We have used a CT-specific in vitro RNA-processing system to identify cis-acting sequences required to prevent splicing to exon 5. Deletion mapping demonstrated the presence of an element within the first 45 nucleotides of the CT-specific exon 4 that was required to suppress splicing to the CGRP-specific exon 5. This element was able to function in a completely heterologous system to suppress splicing when the CGRP exon was replaced with a constitutive viral exon. The element was unable to suppress splicing in the absence of a proximal CT-specific 3' splice site. Our results suggest that CT-specific splicing requires assisted recognition of its 3' splice site.
Mol Endocrinol 1990 Nov
PMID:Calcitonin exon sequences influence alternative RNA processing. 228 Jul 74

The calcitonin (CT) gene is expressed normally in thyroidal C-cells and in a restricted population of cells in the central and peripheral nerve system. To define the cis-elements within the 5'-flanking DNA of the human CT gene which mediate this cell-specific expression, we used DNA transfer techniques and a transient transfection approach. We found that a DNA sequence located between -1290 and -820 of the CT 5'-flanking DNA functioned as an enhancer of basal transcription in C-cells (from medullary thyroid carcinoma) but not in rat glioma (C6), hamster insulinoma (HIT), fibroblasts (3T3), or epithelial cells (HeLa and CV1). Further mapping revealed the presence of at least two elements within the enhancer region; an upstream element (USE, located between -1060 and -1030) which could not function independently but its removal caused 70-80% loss of enhancer activity and a downstream element (DSE, located at -1033 to -920) which functioned independently as a cell-specific enhancer but with reduced activity. The binding pattern of nuclear proteins from C-cells to the enhancer elements was studied by an electrophoretic mobility shift assay. A protein-DNA complex was formed with the USE which could be competed, specifically, by an oligonucleotide containing the microE2 motif of the immunoglobulin gene enhancer. A similar complex was formed with the DSE fragment. Nuclear proteins from HeLa cells failed to form complexes with USE. Moreover, the binding pattern of proteins derived from HeLa cells to DSE was different from that of C-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Nov
PMID:Transcription of the human calcitonin gene is mediated by a C cell-specific enhancer containing E-box-like elements. 228 Jul 75

The structures of some genes of pituitary, hypothalamic and thyroid protein hormones are reviewed. Cys-elements in the 5'-enhancer area of prolactin and growth hormone genes were identified by some authors. The possibility of biosynthesis of two variants of growth hormone and two different biologically active calcitonin related peptides are considered as results of alternative pro-mRNA splicing after expression of growth hormone and calcitonin genes. LH-RH and GH-RH gene structures are presented. They code the primary structures of several peptide hormones with different biological activities. These peptides are released after proteolytic processing of high molecular weight protein precursors. The structural and functional organization of the glucocorticoid receptor is discussed.
Mol Biol (Mosk)
PMID:[Recombinant DNA in the study of protein hormones]. 229 Apr 16


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