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ABSTRACT: Calcitonin, the hypocalcemic hypophosphatemic hormone is produced in the thyroid by the C-cells. We recently detected the presence of calcitonin and its messenger in hepatic tissue in vivo and in vitro. The calcitonin precursor is composed of the N-terminal peptide, calcitonin and a carboxyterminal peptide. We previously reported that in normal human thyroid and in medullary thyroid carcinoma a second calcitonin messenger is expressed in low quantities. This mRNA differs in its 3' region from the first one. It also codes for the N-terminal peptide, calcitonin and a carboxyterminal peptide which differs by the last eight amino acids from the first. We report here that both calcitonin mRNAs are expressed in normal or tumoral liver. Direct estimation, by a specific immunoassay, of the levels of carboxyterminal peptide II, the specific peptide coded for by calcitonin mRNA II, confirmed that this peptide is synthesized in human liver.
Molecular and Cellular Endocrinology 05/1997; 128(1-2):111-5. · 4.19 Impact Factor
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ABSTRACT: Aldosterone significantly enhanced the proliferation of osteoblastic cells from rat calvaria, and this effect was inhibited by RU 26752 and ZK 91587, two antagonists specific to the mineralocorticoid receptor (MCR). In addition, aldosterone inhibited the activity of alkaline phosphatase, a marker of the osteoblastic phenotype, and this effect was also reversed by RU 26752. Cytoplasmic staining of MCR was observed in rat calvaria osteoblasts incubated with a specific polyclonal antiserum raised against rat kidney MCR. This anti-MCR immunoglobulin G immunoprecipitated and macroaggregated the MCR-[3H]RU 26752 complex in osteoblastic cytosol. A single 98-kDa band was observed when osteoblastic cytosol was analyzed by Western blotting with anti-MCR serum. The 98-kDa band was also obtained after autoradiography of irradiated osteoblastic cytosol-[3H]R 5020 complex, and this was abolished in the presence of RU 26752. A p26MR probe, specific to COOH-terminal end of MCR, hybridized with the predicted product after amplification of total cell RNA by polymerase chain reaction technique. Furthermore, hybridization of poly(A)+ mRNA from at calvaria osteoblastic cells with the p26MR probe revealed a major band of approximately 4.2 kb. Collectively, our studies demonstrate the existence of a functional MCR in rat calvaria osteoblasts.
The American journal of physiology 05/1996; 270(4 Pt 1):C1088-95.
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ABSTRACT: Parathyroid hormone related protein (PTHrP) is produced by several breast cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been shown to decrease PTHrP mRNA expression in several cell lines. We therefore tested the in vivo effect of both steroids on PTHrP secretion and tumor development of the Walker carcinoma (WC). WC cells were injected subcutaneously in Fisher rats which were simultaneously treated with either vehicle, or 1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight was significantly decreased in the 2 treated-groups as compared to the control group. Vehicle treated-rats developed hypercalcemia, which was also observed in rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly decreased in the DEX-treated group compared to vehicle-treated rats. In a dose-effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats not implanted with WC, but was required to decrease the tumor weight in implanted rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were significantly decreased, but there was a similar correlation between PTHrP plasma level and tumor weight in the three groups. Indeed, the cytosolic PTHrP content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D decrease WC tumor development in vivo, but do not change the PTHrP secretion by the remaining tumor although steady state PTHrP mRNA content level is decreased by 1,25(OH)2D.
Hormone and Metabolic Research 10/1995; 27(9):403-7. · 2.19 Impact Factor
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ABSTRACT: We recently reported that human liver and primary cultures of hepatocytes express calcitonin. We therefore studied the expression of calcitonin gene related peptide (CGRP), the alternative splicing product of the calcitonin gene, in hepatocytes and liver. We used polymerase chain reaction amplification with specific primers to detect the presence of CGRP I and II messengers and a specific radioimmunoassay to measure the peptide. We report here that CGRP is synthesized by primary cultures of hepatocytes and in liver. As liver also possesses specific receptors for CGRP in non-parenchymal cells, a paracrine system could be involved in liver metabolism.
FEBS Letters 09/1994; 351(1):63-6. · 3.54 Impact Factor
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ABSTRACT: The calcitonin gene family comprises two main genes: CALC I which encodes for calcitonin (CT) mRNA in thyroid and calcitonin gene-related peptide I (CGRP I) mRNA in neuronal tissues and CALC II gene which encodes for CGRP II mRNA only. Recently, in normal thyroid and in medullary thyroid carcinoma (MTC), we detected an additional splicing pathway involving the splicing of exon 4 to exon 5 and leading to the expression of a third CALC I mRNA: CT mRNA II. In the present study, we analyzed by polymerase chain reaction the expression of CT mRNAs I and II, CGRP I and II mRNAs in MTC and in human tumors of the nervous system (3 pituitary adenomas, 3 astrocytomas, 2 schwanomas). In pituitary tissues, CGRP II expression was constant and easily detectable in comparison to other tissues. CT mRNA II signal was very low, but clearly detectable after a reamplification indicating that the factors responsible for the splicing of exon 4 to exon 5 are poorly operative in neuronal tissues.
Neuropeptides 04/1994; 26(3):215-9. · 1.55 Impact Factor
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ABSTRACT: Immunoreactive calcitonin (CT) is present in liver. This could represent hormone synthesized by liver cells, degraded or bound to specific receptors reported in this organ. We report here that the calcitonin gene is expressed in liver. We proved this by demonstrating, by PCR amplification using specific primers, the presence of calcitonin messenger in human liver and in primary cultures of human hepatocytes and detected by radioimmunoassay CT in hepatic tissues and cells. The synthesis of hormone by liver that also possesses specific receptors for CT favors the presence of an autocrine or paracrine system involving calcitonin in this organ.
FEBS Letters 10/1993; 331(1-2):15-8. · 3.54 Impact Factor
