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Biomedical subjects

J M Garel

Publications and source records attributed to J M Garel.

At least 19 recordsLinked to original sources
PubMed1992

Effects of dexamethasone, calcium and 1,25-dihydroxycholecalciferol on calcitonin and calcitonin gene-related peptide mRNA levels from the CA-77 C cell line.

We used the CA-77 cell, a murine C-cell line derived from a medullary thyroid carcinoma, to study the effects of glucocorticoids, calcium, and vitamin D metabolites on calcitonin (CT) gene expression. Total RNA was isolated, and CT and CT gene-related peptide (CGRP) mRNAs were measured by Northern hybridizations using specific probes. A control mRNA probe (cyclophilin) was used to quantitate the specificity of the changes in CT and CGRP mRNAs. The CA-77 C cell line cultured in basal conditions with a medium deprived of fetal calf serum, but was supplemented by insulin, expressed mainly the CGRP mRNA. Dexamethasone was found to increase both CT and CGRP mRNAs in a time- and dose-dependent way without changing the alternative splicing. A slight but significant increase in the steady-state CT mRNA level was found 3 days after addition of 10(-10) M dexamethasone; the same dose slightly decreased the CGRP mRNA level; concentrations of dexamethasone > or = 10(-9) M elevated both mRNAs. A twelve-fold increase for CT mRNA, and an eightfold increase in CGRP mRNA occurred 3 days after administration of 10(-6) M dexamethasone. Kinetic data revealed inductions of both mRNAs 24 hours after exposure to 10(-7) M dexamethasone, and highest CT and CGRP mRNAs levels were observed after 72 hours of treatment. Calcium from 1-4 mM in short-term (1 hour and 4 hour) or long-term stimulations (1 day and 4 days), with or without dexamethasone cotreatment was ineffective. CT and CGRP mRNAs levels were both half-reduced 48 hours after addition of 10(-7) M 1,25-dihydroxycholecalciferol; this effect was transient, as it disappeared 2 days later.

Animals↗
PubMed1991

Effects of 1,25-dihydroxycholecalciferol and calcium on calcitonin mRNA levels in suckling rats.

The chronic administration of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to 9-day-old suckling rats induced no change on day 13 in the calcitonin (CT) mRNA steady-state level of thyroid glands measured by Northern hybridization. Thyroidal CT contents were decreased in relation to increased plasma calcium levels in animals treated with 0.1 or 1 microgram 1,25-(OH)2D3/kg. Using a lower dose (0.01 microgram/kg), neither plasma calcium, nor thyroidal CT contents were changed. No correlation was found between CT mRNA levels and thyroidal CT contents as well as for plasma CT levels and thyroidal CT contents since hormone in blood remained unchanged after treatment by the active vitamin D3 metabolite. Intraperitoneal calcium administration in fasted 13-day-old rats was associated with a 5-fold increase in plasma CT 30 min after injection, but CT mRNA levels were unchanged within 240 min. By contrast, stomach gavage with calcium in fasted 13-day-old rats induced a sustained increase in plasma CT (X2), and a 4-fold increase in the steady-state level of CT mRNA. Calcium per se is a potent stimulator of CT release in suckling rats, but did not change the amount of CT mRNA. However, gastrointestinal factors may be implied directly or indirectly in the increased CT mRNA level after calcium gavage. In conclusion, 1,25-(OH)2D3 which is known to affect CT gene expression in adult rats is ineffective in 13-day-old suckling rats. This observation may be related to developmental changes in the amount of 1,25-(OH)2D3 receptors of C cells.

Animals↗
PubMed1990

Ontogenesis of calcitonin mRNA in the rabbit.

Since plasma calcium levels are higher in the fetus than in the mother at the end of gestation, it has been suggested that calcitonin (CT) biosynthesis would be very active in the fetus. This hypothesis was tested in rabbit fetuses and newborns by measuring the amount of CT mRNAs found in the thyroid glands and the thyroidal CT stores. Dot-blot and Northern hybridizations with a specific CT cDNA probe (a BglII-NsiI fragment of the human CT cDNA) were used to determine the CT mRNA level. In fetuses, newborns, and mothers, only one molecular species of mRNA around 1 kb was detected by Northern hybridization with the specific CT cDNA probe. By dot-blot, CT mRNAs could be detected at 20 days of gestation on pooled fetal thyroid glands as a weak positive signal. The amount of CT mRNAs increased on day 24; at this stage they were also observed by Northern hybridization. During the last 6 days of gestation a 3-fold increase in CT mRNAs occurred in rabbit fetuses; concomitantly a 5-fold rise in the total thyroidal CT content was observed. Fetal plasma concentrations of both CT and calcium increased slightly between 24 and 30 days of gestation. After birth, the CT mRNA level was 10-fold increased between 2 and 30 days; these changes were not reflected in the plasma CT level but were probably accounted for by a rise in the number of C cells of the thyroid gland.

Animals↗
PubMed1990

Dexamethasone increases preproparathyroid hormone messenger RNA in human hyperplastic parathyroid cells in vitro.

To determine if parathyroid hormone release in man is directly stimulated by glucocorticoids, dispersed human parathyroid cells from hyperplastic glands obtained from eight renal transplant recipients were studied in vitro. Dexamethasone (10(-11) to 10(-6) mol l-1) increased PTH release in a time- and dose-dependent manner. A plateau was reached at 10(-8) mol l-1 (1015 +/- 149 vs. 230 +/- 27 pg 10(-4) cells for control value, after 24 h incubation; P less than 0.0001). An interaction with a glucocorticoid receptor was suggested since 10(-6) mol l-1 RU 486 blunted the dexamethasone-induced PTH release. By Northern blot analysis, dexamethasone was found to increase the amount of preproPTH mRNA in these cells. The effect of dexamethasone was probably at the gene level since (1) 1,25 dihydroxy vitamin D3 inhibited both iPTH and preproPTH mRNA increases induced by dexamethasone and (2) alpha-amanitin (1,25 micrograms ml-1) also completely suppressed the dexamethasone-induced PTH release. Thus, for the first time, we demonstrate that dexamethasone induces an increase of PTH synthesis, probably by increasing PTH gene transcription. This effect may play an important pathogenic role in persisting hyperparathyroidism and steroid-induced bone complications in renal transplant recipients.

Amanitins↗
PubMed1979

Immunochemical studies on rabbit calcitonin.

Cross reaction studies using radioimmunoassays specific for human and porcine calcitonin showed that rabbit calcitonin is structurally more closely related to human than to porcine calcitonin.

Animals↗
PubMed1979

Vitamin D-dependent calcium-binding protein. Changes during gestation, prenatal and postnatal development in rats.

During the perinatal period, calcium metabolism is stressed. As intestinal Ca-binding protein is considered as a molecular expression of the hormonal effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3), Ca-binding protin measurements may document the vitamin D roles during this period. We describe the variations of Ca-binding protein concentrations in the rat during the last 5 days of gestation, in the maternal duodenum, placentas, fetal membranes and fetal intestines. We also report intestinal Ca-binding protein changes from birth until weaning. The evolution of the maternal intestinal Ca-binding protein, which increases on day 19.5 of gestation, is consistent with that of calcium intestinal absorption and may be explained by increased 1,25(OH)2D3 production. Placental Ca-binding protein rises from day 17.5 until the end of gestation, and may be related to the profile of calcium transfer from mother to fetuses. It is noteworthy that the placental Ca-binding protein is predominantly found in the fetal part of the organ where materno-fetal exchanges occur. The yolk sac synthesizes substantial amounts of Ca-binding protein. In the fetal membranes, Ca-binding protein plateaus from day 17.5 until day 20.5 and decreases on day 21.5. The Ca-binding protein presence in the fetal placenta and in the yolk sac may suggest that these tissues are also targets for vitamin D. In the fetus the intestinal Ca-binding protein s is detected as early as day 17.5 of gestation and increases markedly during the last day of gestation. From birth and during the first 3 weeks of postnatal life, the intestinal Ca-binding protein concentration does not change. It undergoes a sharp rise just at the time of weaning. We have also shown that the specific distribution of Ca-binding protein along the intestine is acquired during intrauterine life and does not change with sucking or weaning. The two main changes of intestinal Ca-binding protein, observed just before birth and at weaning, may reflect the intestinal maturation and/or variations in vitamin D metabolism.

Aging↗
PubMed1978

[The role of maternal parathyroids and vitamin D3 metabolites in fetal growth and the deposition of glycogen reserves in the maternal and fetal liver in rats].

Thyro-parathyroidectomy of pregnant Rats at 12.5 days of gestation decreased maternal liver glycogen on 21.5 days of gestation and fetal weight as well as fetal liver glycogen stores. The graft of one parathyroid gland or the injection of 1 alpha-hydroxycholecalciferol in these thyro-parathyroidectomized mothers increased their liver glycogen stores at 21.5 days of gestation. These treatments also markedly increased both fetal weight and fetal liver glycogen stores. It was concluded that maternal 1,25-dihydorxycholecalciferol, which is synthesized under the control of parathyroid hormone secretion, controls fetal growth and liver glycogen stores. The mechanism of these effects (direct or indirect) requires further investigations.

Animals↗
PubMed1978

[Stimulation of calcitonin secretion in the fasting newborn rat by ingestion of triglycerides].

The stomach gavage of fat (triglycerides) in the fasting newborn Rat induced a marked increase in the plasma concentration of immunoreactive calcitonin after 30 and 60 mn. Calcium chloride given by the same route at the dose of 20 mg calcium per kg body weight had a poor effect on calcitonin secretion. This stimulation was probably mediated through some gastro-intestinal hormone that has to be uncovered.

Animals↗
PubMed1977

Plasma parathyroid hormone and calcitonin levels in hypocalcaemic magnesium-deficient calves.

Mg deficiency was experimentally induced in 3 calves given Mg-deficient semi-synthetic milk (10 mg of Mg/l of milk). Three control calves received the same milk supplemented with Mg (190 mg of Mg/l of milk). Calcium and vitamin D contents of this milk were similar to that of natural milk. Daily weight gain in control calves was similar to that observed in calves given natural milk. The daily weight gain of Mg-deficient calves was not statistically different from that of control calves during the first 6 weeks of Mg-deficiency. Then clinical symptoms of Mg-deficiency appeared (loss of appetite, nervousness, tetany crises). In these Mg-deficienct animals a fall in plasma magnesium level, followed by hypophosphataemia and then by hypocalcaemia was observed. During the whole experimental period plasma CT and plasma PTH levels were not statistically different in Mg-deficient and in control calves. These results show that the hypocalcaemia observed in Mg-deficient calves was due neither to an increase in CT secretion nor to a decrease in PTH secretion. Nevertheless, the parathyroid glands from these animals seem unable to react satisfactorily to the hypocalcaemia induced by Mg-deficiency.

Animals↗
PubMed1976

Calcium metabolism in newborn animals: the interrelationship of calcium, magnesium, and inorganic phosphorus in newborn rats, foals, lambs, and calves.

The plasma concentrations of calcium, inorganic phosphorus, and magnesium were studied during the early postnatal period in a rodent (rats), in ruminants (lambs and calves), and in foals. Decreases in plasma calcium after birth were observed only in newborn rats and foals. In rats the postnatal fall in plasma calcium level was already evident 1 hr after cesarean section (9.20 mg/100 ml) as opposed to 11.90 mg/100 ml in utero) and reached a nadir within 6 hr (-4.05 mg/100 ml). Newborn foals showed a small decrease in plasma calcium (-0.73/100 ml) 48 hr after birth. In the four species plasma inorganic phosphorus increased in the days after birth; plasma magnesium levels were only slightly affected over the first week of life. In ruminants and in foals, the high plasma calcitonin levels were not always related to plasma calcium, nor with plasma inorganic phosphorus over the first week of life. Newborn calves showed at birth detectable levels of plasma parathyroid hormone, similar to those found in their mothers, with individual values ranging from 0.80-3.50 ng/ml. These results are discussed in light of the well known early neonatal nypocalcemia occurring in normal human newborns.

Animals↗
PubMed1976

A radioimmunoassay for bovine parathyroid hormone.

A radioimmunoassay for bovine parathyroid hormone (bPTH) has been developed. An antibody was raised in a goat against 1-84 b PTH which was directed against the carboxy-terminal part of the molecule (no cross-reactivity with synthetic 1-34 b PTH fragment). 1-84 b PTH was labelled with 125I using the chloramine-T method. The tubes were incubated at 4 degrees C for 6 days in an equilibrium system with 25% protein concentration. Separation was performed using plasma-coated charcoal. Jugular venous plasma PTH levels were shown to be increased in hypocalcemic parturient cows.

Animals↗
PubMed1975

Plasma immunoreactive calcitonin levels in pregnant mares and newborn foals.

Plasma calcium and calcitonin levels were measured periodically during the two last months of pregnancy and at the time of parturition in 9 pregnant mares and their foals. In pregnant animals, there was an increase in plasma calcitonin levels in the days before parturition, which was not due to any change in plasma calcium. This result indicates that in the mare, as in the cow, in the days before parturition CT secretion escapes from its control by plasma calcium. In 0-day and 7-day-old foals plasma calcium levels were significantly higher than in their mothers, but plasma calcitonin levels were not significantly different from those observed in their dams at the time of parturition.

Animals↗
PubMed1975

Metabolic effects of calcitonin in the newborn.

Calcitonin was injected in newborn rats and newborn lambs to study the metabolic effects of the hormone. Subcutaneous injection of salmon calcitonin (140 MRC U/kg) induced a clearing effect on plasma from suckling newborn rats that was naturally lactescent. A lower dose given by the same route (14 MRC U/kg) strongly decreased plasma triglyceride and amino acid levels in suckling newborn rats. This was mainly the result of gastric emptying inhibition. The gastrointestinal action of calcitonin in suckling newborn rats was substantiated by the absorption of [14C]triolein and 14C-labeled amino acids. Hormonal changes that were associated were a decrease in plasma insulin level and an increase in plasma growth hormone concentration. Intravenous calcitonin at a physiological dose (0.03 MRC U/kg) injected into newborn lambs inhibited increases in total plasma lipids, amino acids, and blood-glucose levels at the time of the first suckling period without changing serum calcium levels. One of the physiological roles of calcitonin in the newborn may be the regulation of nutrient absorption from milk rich in lipids.

Amino Acids↗