Acute responsiveness to calcitonin in chronic renal failure.

The acute effect of porcine calcitonin was tested in 17 patients undergoing chronic haemodialysis. In normal adults calcitonin has no effect on plasma calcium or phosphate levels, but in nine patients both concentrations were substantially reduced after calcitonin. This hypocalcaemic and hypophosphataemic effect was a function of the initial plasma phosphate level but was unrelated to the initial plasma calcium level. Plasma hydroxyproline levels were not significantly different in the two groups an were unaffected by calcitonin. In 11 patients fasting plasma calcitonin levels were undetectable with an assay sensitive to 0-1 mug/1. Calcitonin seems to have an acute effect in chronic renal failure which may not operate by arresting bone resorption but is dependent on the plasma phosphate concentration.     

Serum levels of calcitonin, parathyroid hormone and 25-hydroxycholecalciferol in patients with diabetes mellitus

Blood serum levels of calcitonin, parathyroid hormone, calcium, magnesium and inorganic phosphate have been measured in basal condition and following intravenous administration of calcium in 31 patients with diabetes of type I, in 31 patients with diabetes of type II and in 29 healthy subjects. The level of 25-hydroxy cholecalciferol was measured in all these patients in basal condition only. It was found that the basal calcitonin level was significantly higher in patients with both types of diabetes than in healthy subjects. The administration of calcium caused a significantly higher increase in the blood calcitonin level in patients with type I diabetes than in those with type II diabetes. It was found in addition that in women with type II diabetes blood serum level of parathyroid hormone was significantly higher than that in men suffering from diabetes of the same type, suggesting the participation of some sex-related factor in the pathogenesis of the abnormal parathyroid level in these patients.     

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.     

Plasma calcium and calcitonin in the marine teleost, Gadus morhua

Total, free and ionic plasma levels of calcium as well as total plasma magnesium and inorganic phosphate levels were studied in the Atlantic cod, Gadus morhua, in relation to salmon calcitonin injections. Plasma ion levels and endogenous levels of calcitonin were studied during environmentally induced hypercalcemia. It is concluded that no apparent relationship between calcitonin and calcium levels was found, and it is implied that calcitonin in fish may have a physiological function not related to blood calcium regulation.     

Effect of infusion of salmon calcitonin on the secretion of somatostatin and gastrin in man

In vitro and animal studies have pointed out complex interrelations between gastrointestinal hormones and calcitonin. To analyse the acute effects of calcitonin in more detail, patients undergoing surgery were infused intravenously with synthetic salmon calcitonin, a potent analog of the human hormone. Samples were taken after 0, 30 and 60 minutes from the hepatic, portal and a peripheral vein. Somatostatin and gastrin were determined by radioimmunoassay. The mean basal levels of somatostatin in peripheral and hepatic venous plasma (14.2 and 15.6 pg/ml) were significantly lower than in portal plasma (45.6 pg/ml), indicating effective removal by the liver. After infusion of calcitonin there was a general rise in somatostatin levels and an increase in the gradient between hepatic and portal blood. Basal gastrin levels were highest in the portal vein when compared intraindividually. The differences disappeared after calcitonin infusion with a concomitant systemic reduction of gastrin levels. Thus, calcitonin is able to stimulate the secretion of somatostatin from the gastrointestinal tract and does reduce gastrin secretion, possibly via the stimulation of somatostatin secretion.     

Plasma calcitonin response to a calcium clamp. Influence of sex and age

The influence of sex and age on basal and calcium stimulated immunoreactive plasma calcitonin (iCT) were studied in 36 healthy subjects. An identical calcium stimulus, "calcium clamp", was applied to 10 young males, 13 premenopausal females of similar ages and 13 postmenopausal females. A significantly greater iCT response was found in males compared with both female groups. No age correlation in basal or calcium stimulated iCT levels was observed despite 35 years difference in mean age between the pre- and postmenopausal groups. A positive correlation between the induced change in whole blood ionized calcium (B-Ca++) and the iCT response, recorded after 15 min, was seen in young subjects of both sexes. Basal iCT and B-Ca++ were similar in all three groups. No correlation between basal iCT and basal B-Ca++, or between basal iCT and age was found. The total amounts of infused calcium per kg body weight were equal. The results indicate that male subjects have a greater secretory capacity of the thyroid C-cell than females. No reduction of the secretory capacity was observed with increasing age in females, neither was any difference found between pre- and postmenopausal females of the iCT-response.     

Bisphenol A influences the plasma calcium level and inhibits calcitonin secretion in goldfish

In teleosts, it is well known that plasma calcium levels increase as a result of treatment with estrogen for at least during 2 weeks and that calcitonin secretion is induced by estrogen. The present study examined the influence of bisphenol A on calcium homeostasis in goldfish and compared the above known estrogenic action. In goldfish kept in water containing bisphenol A (10(-6) M), the plasma calcium concentration increased significantly (P<0.001) at 4 days but decreased significantly (P<0.05) at 8 days. By the treatment of bisphenol A, calcitonin secretion was not induced until 4 days. At 8 days, however, plasma calcitonin, as well as calcium, decreased significantly (P<0.05), although vitellogenin was detected in the plasma. Therefore, bisphenol A influences plasma calcium levels, but its action is different from that of estrogen, which indicates that bisphenol A affects the calcium homeostasis and might bring about abnormal conditions in teleosts.     

Adaptation of rainbow trout (Salmo gairdnerii) to sea water: Changes in calcitonin levels

• 1.1. The calcitonin content of the ultimobranchial body (UBB) and plasma levels of calcitonin, calcium and phosphate were measured in rainbow trout (Salmo gairdnerii) following their transfer from fresh to sea water.
• 2.2. The plasma calcium level remained unchanged throughout the experiment while the UBB calcitonin content, plasma calcitonin and plasma phosphate rose significantly during the hours immediately following transfer.
• 3.3. The levels of all three subsequently fall so that, 8–15 days later, a new equilibrium was established with lower than control (fresh water) levels of UBB calcitonin, plasma calcitonin and plasma phosphate.
• 4.4. It would appear, from these data, that calcitonin plays some part in the endocrine regulation of sea water transfer.

     

A dual effect of calcitonin gene-related peptide on plasma calcium levels in the chick

Calcitonin gene-related peptide (CGRP) lowers plasma calcium in the rat and inhibits bone resorption by isolated rat osteoclasts. In our preliminary studies we found that rat CGRP elevates plasma calcium levels in the chick, a response that was somewhat similar to that of parathyroid hormone. Here, we report that human CGRP (alpha) produces a concentration-dependent elevation of plasma calcium levels. The two peptides did not follow precisely the same time course. Whereas at 15 minutes CGRP produced hypocalcaemia relative to the control plasma calcium levels, at 30 minutes both CGRP and PTH were found to be hypercalcaemic. These studies suggest that CGRP initially interacts with the calcitonin receptor to produce a calcitonin-like effect, which is followed by hypercalcaemia presumably by antagonising the action of endogenous circulating calcitonin.     

Plasma immunoreactive calcitonin in lung cancer.

We have measured plasma calcitonin in 135 untreated eucalemic men with lung cancer and a control/smoker population. Calcitonin levels were determined by radioimmunoassay and validated by immunoextraction. Plasma immunoreactive calcitonin moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human calcitonin radioimmunoassays of cancer-patient plasmas were detected by parallel plasma incubations in a salmon calcitonin radioimmunoassay system which does not detect human calcitonin and by immunoprecipitation of tracer at the end of radioimmunoassay incubations. Heating fresh plasmas to 65 degrees C for 1.5 hours reduced radioimmunoassay artifacts without loss of calcitonin moieties. Such characterization of hypercalcitoninemia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma calcitonin radioimmunoassay measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma calcitonin seemed to be elevated in 18% (14/80) of basal plasma samples obtained from patients with epidermoid or with anaplastic lung cancer. Unequivocal hypercalcitoninemia (heat stable, causing no inhibition of antibody-tracer binding in the salmon calcitonin radioimmunoassays, and immunoextractable with human calcitonin antibodies) was not found in any of the apparently hypercalcitoninemic plasmas from persons with epidermoid or anaplastic lung cancer. By contrast, unequivocal hypercalcitoninemia was found in 27% (15/55) of plasmas from patients with small cell carcinoma or adenocarcinoma. Most of the immunoreactive calcitonin recovered from small cell and adenocarcinoma lung cancer plasmas with unequivocally elevated calcitonin is much larger than calcitonin monomer.     

Relationship of blood concentrations of calcium, phosphate, gastrin and calcitonin to the onset of feeding in the rat.

Daily fluctuations in plasma calcium concentrations in rats trained to a closely regulated feeding pattern have been compared to corresponding plasma gastrin and calcitonin concentrations. The time period studied was that extending from 4 hr prior to the start of the feeding. Both plasma calcium and phosphate levels fedd prior to the start of the feeding period and remained low at least for the first 2 hr of feeding. This pattern was also observed in rats in which food was withheld for 2 hr past the regular feeding time. Plasma 45Ca and 32P concentrations (radionuclide injected at least one week prior to sampling) did not follow the pattern of their stable counterparts. Instead, these values rose or remained constant until after feeding had commenced, after which they fell precipitously. Both plasma calcitonin and gastrin levels rose rapidly after the start of the feeding period. The primary point of emphasis is that calcitonin secretion was produced in these rats by an intestinal related stimulus and not by a rise in plasma calcium concentration.     

Influence of somatostatine on plasma level of calcitonin in the calf and the swine]

In young calves receiving intraveinously a small dose of calcium to stimulate calcitonin release, intraveinous infusion of somatostatin did not significantly modify the jugular veinous plasma calcitonin levels measured by radioimmunoassay, using a porcine system which cross-reacts with bovine calcitonin. In piglets, intraveinous infusion of somatostatin also did not change the jugular veinous plasma calcitonin concentration.     

Calcitonin secreting property of ipriflavone in the presence of estrogen

Calcitonin secretion is influenced by estrogen. In the present study, basal and calcium-stimulated serum calcitonin levels were reduced in ovariectomized rats, and replacement estrogen administered for 3 weeks increased both calcitonin levels to those in intact rats. Ipriflavone, 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one, alone did not influence either calcitonin level. However, ipriflavone and subeffective doses of estrogen administered simultaneously increased both levels; the increase depended upon the dose of ipriflavone. Furthermore, pretreatment with estrone resulted in greater calcitonin release in response to various doses of calcium and pretreatment with estrone and ipriflavone caused an even greater release. These findings indicate that ipriflavone increases the sensitivity of the thyroid gland to estrogen to secrete calcitonin in response to calcium.     

Plasma immunoreactive calcitonin in the frog (Rana pipiens)

1. Plasma immunoreactive calcitonin (iCT) and ionic calcium [( Ca]i) were measured in intact frogs (Rana pipiens) within complete 24 hr light-dark cycles over an 18 month period. 2. Plasma iCT exhibits an annual periodicity about the annual mean of 10.0 ng/ml, with an amplitude of 5.4 ng/ml that peaks in October. 3. Within an annual cycle, a significant inverse association exists between the basal monthly levels of plasma iCT and [Ca]i for animals maintained in freshwater control conditions. 4. When subjected to a high calcium environment during the latter half of the year, plasma [Ca]i and iCT were elevated above control levels but exhibited independent cyclic patterns. 5. A distinct seasonal response of increased iCT in a high calcium environment may be related to the secretory activity of the ultimobranchial glands and physiological responsiveness to other calcemic hormones; e.g. parathyroid hormone and vitamin D.     

Blood calcitonin in alcoholic cirrhosis]

In spite of an important metabolic role of the liver in the synthesis and degradation of hormonal peptides and seco-stero?ds, the clinical occurrence of disturbed regulation of calcium and phosphorus metabolism is rare in hepatic disorders. 23 patients suffering from alcoholic cirrhosis were studied. All had normal plasma calcium and phosphorus concentration as well as immunoreactive parathyroid hormone levels. 25 hydroxyvitamin D3 levels were decreased. Immunoreactive calcitonin were increased in relation to the increase in plasma alkaline phosphatase activity. The causes and consequences of these endocrine disturbances are discussed.     

Elevated levels of calcitonin mRNA: a marker for the spontaneous development of medullary thyroid carcinoma in rats

The aging WAG/Rij rats (a Wistar derived strain) develop spontaneously medullary thyroid carcinoma with a high frequency (50%). We have studied calcitonin biosynthesis in Wistar and WAG/Rij rats strains in order to determine if early changes in this parameter occurred in the WAG/Rij strain. Thyroidal and plasma CT levels were measured in three months old WAG/Rij and Wistar rats before and after acute calcium challenge. Total RNA was extracted from thyroid glands and specific CT messenger RNA levels estimated by dot and Northern blot analysis with a 32P-labeled probe specific for CT mRNA. The capacity of mRNA to direct synthesis of CT precursor was also measured by translation in an in vitro system. Though mean basal circulating CT levels were equivalent in both strains, CT release after calcium stimulation was much increased in the WAG/Rij rat. CT content of the glands and CT mRNA levels were two fold higher in the WAG/Rij strain. Thus, in this strain, CT biosynthesis and secretion were increased long before the development of a C-cell carcinoma.     

Effect of short- and long-term stress on plasma calcium and calcitonin in the rat

Although hypocalcemia has been observed during stress, the cause(s) is still unknown. The effect of short- and long-term restraint stress on calcitonin (CT) secretion and on plasma calcium (Ca), inorganic phosphate (P), total protein (TP), and corticosterone (CORT) were investigated in the male and female Sprague-Dawley rat. The rats were restrained in the supine position for two hours/day for either one day (STS) or for 14 days (LTS), and compared to normal controls (CON). Plasma Ca levels in both STS and LTS rats were significantly lower and mean plasma CORT levels in female stressed rats were significantly higher than those in sex-matched CON rats. However, mean basal levels of plasma CT did not differ among these three groups for either sex. Similarly, mean increment of plasma CT after Ca infusion (Ca 10 mg/100 g, i.v.) did not differ between STS or LTS rats and CON rats. These data reveal no causal relationship between CT and the hypocalcemia during either short-or long-term stressful stimuli.     

The effects of calcitonin on calcium uptake and respiration in rat-liver mitochondria

The action of calcitonin on both the transport of calcium across the mitochondrial membrane and cellular respiration has been studied in the presence and absence of added phosphate. In the presence of phosphate, both the rate of calcium entry and the amount of calcium accumulated was stimulated by calcitonin, above a threshold concentration, in a saturable manner. In the absence of phosphate, calcitonin enhanced the rate of calcium entry, but had no appreciable effect on the levels of total calcium accumulated. The minimum concentration of calcitonin necessary to produce these effects was in all cases dependent on the external calcium concentration. Mitochondrial respiration was inhibited only at calcitonin levels much higher than those affecting calcium uptake. These results are consistent with the idea that the action of calcitonin is directly related to the mechanism of calcium uptake, and not to the respiratory process.     

Biological actions of human and rat calcitonin and calcitonin gene-related peptide

We assessed the central and peripheral biological actions of human and rat calcitonin and calcitonin gene-related peptide (CGRP). After intravenous administration, human and rat calcitonin, but neither human nor rat CGRP significantly decreased plasma calcium and phosphorus concentrations in awake, freely moving rats. After intracerebroventricular as well as after intravenous administration, human and rat calcitonin and human and rat CGRP significantly inhibited gastric acid secretion in conscious rats. Intracerebroventricular administration of rat calcitonin did not alter plasma calcium and phosphorus concentrations. Linear, partially protected CGRP and calcitonin did not exhibit any biological effects. These studies indicate that calcitonin, but not CGRP, affects calcium and phosphorus homeostasis while both peptides decrease gastric acid secretion similarly. Furthermore, these studies support the hypothesis that the calcium and phosphorus lowering effects of calcitonin are peripheral while the gastric inhibiting actions of the calcitonin and CGRP are mediated by the central nervous system.