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P Besnard

Publications and source records attributed to P Besnard.

50 records · Page 3Linked to original sources

Increased level of calcitonin mRNA after 1,25-dihydroxyvitamin D3 injection in the rat.

Vitamin D metabolites are able to change plasma calcitonin (CT) levels, but nothing is known about a possible effect at the CT gene level. Here we have investigated the acute effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the CT biosynthetic activity of thyroid glands from adult rats. Plasma CT levels were significantly increased (X2) 1 and 2 h after 1,25-(OH)2D3 injection in the face of unchanged plasma calcium values. The thyroidal CT content also was unchanged. A 2-fold increase in CT mRNA level measured by dot-blot hybridization occurred 1 and 2 h after 1,25-(OH)2D3 administration. Expression of CT gene products was examined in the rabbit reticulocyte lysate cell-free translation assay. After polyacrylamide gel electrophoresis, specific immunoprecipitates were autoradiographed and quantified by integration. A single precursor of Mr approximately equal to 15 000 could be specifically immunoprecipitated with CT antisera. A 3-4-fold rise in translatable CT mRNA activity was observed 1 and 2 h after 1,25-(OH)2D3 injection. Thus, parallel changes in CT mRNA level, CT mRNA activity and plasma CT levels were observed in adult female rats after administration of 1,25-(OH)2D3. These findings demonstrate for the first time that 1,25-(OH)2D3 enhanced CT gene expression in the face of unchanged plasma calcium levels.

Animals↗

Effects of cold exposure on calcitonin secretion in the young rat.

The effects of cold exposure on calcitonin (CT) secretion were evaluated in young rats. Acute cold exposure (5 h to 5 degrees C) induced a rise in plasma CT concentrations and a decrease in thyroidal CT stores without change in total and ionized plasma calcium levels. The cold activation of sympathico-adrenomedullary axis and the inhibition of CT response to cold after beta-antagonist treatment might suggest that endogenous catecholamines can enhance CT secretion in young rats. Cold adaptation (3 weeks to 5 degrees C) induced a fall in plasma calcium concentration and a rise in thyroidal CT stores without change in plasma CT levels. The high plasma glucocorticoid levels which are known to occur during chronic cold exposure could be involved in the rise of thyroidal CT content in cold adapted rats.

Adaptation, Physiological↗

[Plasma concentrations of immunoreactive calcitonin in rats during lactation].

A mild hypocalcemia (0.5 mg/dl) is observed in rats after 14 days of lactation, but plasma and thyroidal calcitonin (CT) levels are both increased on day 7 of lactation. Plasma CT levels are higher (x2) in lactating females than those found in virgin females from day 7 to the end of lactation (21 days). In vitro, the CT secretion rate after calcium stimulation(3 mM) is not different between lactating and virgin females. The rapid removal of pups after parturition in control females induces a rebound in plasma calcium (+1.4 mg/dl) and plasma phosphate (+1.6 mg/dl) associated with elevated plasma CT values. Our results suggest, that the transient mild hypocalcemia of lactation is preceded by increased plasma CT levels; and that it is not the cause of elevated plasma parathyroid hormone levels already reported by us.

Animals↗

[Effect of 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol on thyroid calcitonin content in the suckling or weanling rat].

We have examined the effects of vitamin D3 metabolites on plasma calcium, plasma calcitonin (CT) and thyroidal CT contents in Rats before and after weaning. A daily injection of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3; approximately 25 pmoles/Rat/day during 4 days] induced a marked rise in plasma calcium (16.1 +/- 0.2 vs. 11.3 +/- 0.3 mg/dl in controls) and a great decrease in thyroidal CT content (-70% of control values) in 13-day-old suckling baby Rats, while no change occurred in response to 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) administration. A negative correlation between plasma calcium level and thyroidal CT stores was found in suckling and in weaning Rats treated with different doses of 1,25-(OH)2D3. The significant difference between the slopes of the two regression lines demonstrated a greater mobilization of the CT stores in weaning than in suckling Rats in response to a given hypercalcemia. Our results could suggest that 24,25-(OH)2D3 at the dose used, does not regulate CT secretion while 1,25-(OH)2D3 has probably an indirect effect on CT release, but in vitro experiments will be performed to confirm this hypothesis.

24,25-Dihydroxyvitamin D 3↗

[Perifusion study of the secretion of calcitonin in the young rat: effect of isoproterenol and theophylline].

A perifusion system was used to study the calcitonin secretion during development in the Rat. In this preliminary report, we have shown that calcitonin secretion increased in response to isoproterenol and theophylline in 14-day-old suckling baby Rats. This method provides a sensitive in vitro system for studying factors which may affect calcitonin release during the perinatal period in the Rat.

Aging↗

Fetal growth and 1,25-dihydroxyvitamin D3 injections into thyroparathyroidectomized pregnant rats.

Thyroparathyroidectomy (TPTX) in pregnant rats on day 12.5 of gestation was associated with a progressive reduction of dietary intake between days 18 and 21 of gestation. In control mothers with a similar dietary restriction, the fetal plasma calcium and phosphate levels were unchanged, and a slight decrease in fetal weight (approximately 0.8 g) was observed at term. Maternal hypocalcemia in TPTX animals induced chronic fetal hypocalcemia beginning at day 18.5 of gestation; fetal hyperphosphatemia was only statistically significant on the last day of gestation. Weight, blood glucose and liver glycogen stores, which were greatly decreased in fetuses from untreated TPTX mothers, increased after injection of 1,25-(OH)2D3 into TPTX mothers. A marked increase in fetal weight (+ 1.6-2.0 g) occurred at term with doses ranging from 0.05 to 0.25 micrograms/kg of body weight; higher doses (greater than or equal to 0.5 micrograms/kg) inhibited this improvement. Fetal blood glucose was normalized (approximately 45-50 mg/100 ml) when TPTX mothers received 0.05 to 0.5 micrograms/kg, but decreased with higher doses. The highest fetal liver glycogen store (80 mg/g) was achieved using 0.05 micrograms of 1,25-(OH)2D3/kg, this increment being progressively inhibited when larger doses were given. Subcutaneous calcifications were observed in the fetuses of some litters after treatment of the TPTX mothers with 1 microgram of 1,25-(OH)2D3/kg.

Animals↗

C cell activity during the prenatal and postnatal periods in the rat.

The high plasma calcitonin (CT) level found in suckling newborns and baby rats led us to hypothesize that thyroid C cells might be exhausted during the postnatal period. This prompted us to evaluate the CT concentration of the thyroid C cells during the prenatal and postnatal periods in the rat as the CT content to number ratio of C cells. The CT content of the thyroid gland increased exponentially from 17.5 (0.03 ng) to 21.5 (1.72 ng) days of gestation in the rat fetus; C cells were detected by immunofluorescence and counted from 19.5 days of gestation until term. A value of 600 + 90 C cells was obtained at 19.5 days, 1557 +/- 239 at 20.5 days, and 2602 +/- 536 at 21.5 days of gestation. Plasma CT concentrations were undetectable (less than 150 pg/ml) before 20.5 days of gestation, but increased to approximately 500 microgram/ml in 20.5- and 21.5-day-old fetuses. After birth, both the thyroid CT content and the number of C cells increased progressively. In 3-day-old suckling newborns, 4298 +/- 412 C cells were found; 9679 +/- 1114 were found 7 days after birth, and 12202 +/- 1280 were observed 15 days after birth; at the same stages, the CT contents of the thyroid gland were 6.54 +/- 0.18, 8.59 +/- 0.19, and 19.49 +/- 0.79 ng, respectively. Thus, the CT concentrations of the C cells (approximately 1.0 pg/cell) were roughly similar during the prenatal and postnatal periods in the rat. These results suggest the presence of active C cells during fetal life in the rat. They also indicate a capacity of C cells during the prenatal and postnatal periods to increase their secretion of CT while maintaining their hormone content, since the CT concentration of the C cell remains unaltered in spite of the high CT secretion in suckling rats.

Animals↗

Research of an in vitro model to study the expression of fatty acid-binding proteins in the small intestine.

In order to find an in vitro model for studying the regulation of the biosynthesis of the cytoplasmic Fatty Acid-Binding Proteins (FABPc) expressed in the small intestine, Intestinal- and Liver- (I- and L-) FABPc expressions were tested by Northern blotting in 8 normal or cancerous intestinal cell lines from man, mouse and rat and in organ culture of mouse jejunal explants. Neither I- nor L-FABPc mRNA was detected in any cell strains tested except in the highly differentiated human enterocyte-like intestinal cell line Caco-2. In this line, Northern blot analysis revealed a single messenger of about 0.7 kb corresponding to the L-FABPc. A two-fold increase in mRNA L-FABPc occurred in differentiated Caco-2 cells treated for 7 days with 0.05 mM bezafibrate, a peroxisome-proliferating hypolipidemic drug. The lack of I-FABPc messengers in this strain led us to seek another in vitro model. I- and L-FABPc messengers were found using an organ culture of mouse jejunal explants. A clear rise in I- and, especially, L-FABPc mRNA levels occurred 6 and 24 hr after the addition of 0.05 mM bezafibrate in the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of gene expression by fatty acids: special reference to fatty acid-binding protein (FABP).

During the last years, the direct involvement of lipidic nutrients in the regulation of genes has been established. Fatty acids may induce or repress the transcription rate of several genes involved in both lipid and carbohydrate metabolisms. Gene up-regulation has been found in various tissues including liver, adipose tissue and small intestine. It is only triggered by saturated and unsaturated long-chain fatty acids or their CoA-derivatives. In contrast, gene down-regulation appears to be restricted to the liver. This negative effect is exerted only by polyunsaturated fatty acids. Long-chain fatty acids are able to regulate the expression of two different genes oppositely in the same cell type. The molecular mechanism of these fatty acid-mediated effects remains unclear. The involvement of members of the peroxisome proliferator-activated receptor is discussed.

Adipocytes↗

1,25-Dihydroxycholecalciferol effects on plasma calcitonin levels and calcitonin mRNA in normal or partially vitamin D-depleted rats.

The physiological effect of 1,25-(OH)2D3 on the regulation of calcitonin (CT) secretion was studied by measuring plasma CT levels and CT mRNAs extracted from thyroid glands of normal (D+) or partially vitamin D-depleted rats (D-). In both groups, acute 1,25-(OH)2D3 administration of 0.1 microgram/kg b.w. yielded an early drop in plasma calcium concentrations (around 0.6-1 mg/dl) with a maximum decrease 15 min after treatment. In spite of this hypocalcemia, a significant rise in plasma CT levels was observed within 5 min in D+ animals and within 30 min in D- animals after injection of the vitamin D metabolite. Nevertheless, the increased CT secretion was not associated with a marked and sustained rise in CT mRNA levels measured by dot-blot hybridization or CT mRNA activity evaluated by translation assay. By contrast to the observations made previously using supra-physiological doses of the vitamin D metabolites, no clear-cut effect on CT mRNA levels was found with lower doses. If we hypothesized that 1,25-(OH)2D3 plays a physiological role in CT secretion, our results suggest that this rapid control could be exerted at a post-translational level may be via an increase in the cytoplasmic ionized calcium concentration of C-cells.

Animals↗

Calcitonin secretion during postnatal development in the rat: beta-adrenergic agents and vitamin D3 metabolites.

The possible contribution of catecholamines and vitamin D3 metabolites to the high plasma calcitonin (CT) levels in suckling baby rats is unknown. So, in vivo and in vitro (using a perifusion system) effects of beta-adrenergic agents and vitamin D3 metabolites on CT release were studied in the rat during the postnatal development. In 13-day-old rats, the increase in plasma CT levels induced by isoproterenol injection (0.1 micrograms/kg b.w.) was inhibited by a previous administration of propranolol. A significant decrease in plasma CT levels was observed after propranolol injection in baby rats (0.68 +/- 0.05 ng/ml vs. 0.93 +/- 0.01 ng/ml). A daily injection of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3; 25 pmoles/rat/day during 4 days) induced a marked rise in plasma calcium (16.1 +/- 0.2 mg/dl), and a great decrease in thyroidal CT contents (approximately 70% of control values) in 13-day-old rats while no change was noted with 24,25-dihydroxycholecalciferol (24,25-(OH)2D3). A negative correlation between plasma calcium and thyroidal CT stores was found in suckling and in weaning rats treated with different doses of 1,25-(OH)2D3, suggesting an indirect effect of 1,25-(OH)2D3 on CT secretion. The mobilization of the thyroidal CT content was greater in weaning than in suckling rats in response to a given hypercalcemia. In vitro, 5 X 10(-5) M isoproterenol induced a rapid increase in CT secretion rate while 1,25-(OH)2D3 inhibited the rise in CT release induced by 3.0 mM calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗

Biphasic calcitonin release in the newborn rat.

A sustained elevation in plasma calcium levels was induced in 2-h-old fasted newborn rats by gavage of calcium (200 mg Ca/kg body weight). Plasma calcium was already increased 2 minutes after gavage (1.2 mg/100 ml) and subsequently raised until 30 minutes (13.15 +/- 0.15 mg/100 ml versus 7.70 +/- 0.30 mg/100 ml in controls: gavage with saline only). Then, a slow decrease in plasma calcium levels was observed 60 and 90 minutes after gavage. In response, a peak in plasma calcitonin concentrations occurred 5 minutes after gavage (1.25 +/- 0.10 ng/ml verus < 0.3 ng/ml in controls); plasma calcitonin levels fell from 5 to 30 minutes after gavage and raised again 60 and 90 minutes after gavage. Plasma phosphate levels were decreased from 30 to 90 minutes after calcium gavage, may be in relation to the increased calcitonin secretion.

Animals↗