Porcine Calcitonin Research Articles

Hypocalcemic effect of pentagastrin and related gastrointestinal hormnal peptides in the rat.

The hypocalcemic effect of gastrointestinal hormonal peptides was evaluated in young fasted rats. Systemic iv injection of synthetic pentagastrin and tetragastrin and of native porcine gastrin in doses of 4-12 μg/rat produced modest hypocalcemia (fall of 6-12%) IS and 30 min later. By 60 min after injection normocalcemia was reestablished. Single injections of pentagastrin produced hypophosphatemia as well as hypocalcemia. The hypocalcemic effect of pentagrastrin was abolished after acute removal of the thyroid gland, suggesting that the secretion of thyrocalcitonin (TCT) was involved. This interpretation also was supported by the fact that the magnitude and duration of hypocalcemia produced in rats by iv gastrointestinal peptides could be mimicked by a small (0.25 mU) iv dose of porcine TCT. In related experiments, multiple iv injections of pentagastrin at 30-min intervals into intact rats failed to maintain the hypocalcemic effect observed 30 min after a single injection. Injection of a high dose of bet...

The Effect of Porcine Calcitonin on Osteoporosis Induced by Adrenal Cortical Steroids

Effects of porcine calcitonin (five MRC units per kilogram per day) on development of osteoporosis induced by cortisone (fifteen milligrams per kilogram per day) have been investigated in adult rabbits. Measurements of surface undergoing resorption and formation were determined from cross sections of femoral mid-diaphyses, femoral metaphyses, ribs, and vertebral bodies using the quantitative microradiographic method of Jowsey. Intact femora and vertebral bodies were evaluated for gross rarefaction by high resolution macnoradiography. Bone mass per unit area was determined and mineral content of femora, ribs, and vertebrae was esimated by ashing. Cortisone treatment alone: (1) decreased bone formation and increased bone resorption at all skeletal sites evaluated, (2) decreased the amount of bone mass per unit area in both cortical and cancellous specimens, (3) caused gross macroradiographic rarefaction of femora and vertebral bodies, and (4) reduced the ash weight of ribs and vertebrae. Calcitonin treatment alone: (1) increased bone formation in cortical specimens and reduced bone resorption in vertebral bodies, (2) caused increased density of metaphyseal zones of vertebral bodies as shown by macroradiognaphy, and (3) increased the ash content of femora, ribs, and vertebrae. When compared with specimens removed from animals receiving only cortisone, specimens removed from animals receiving both hormones exhibited: (1) reduction in bone resorption rates in the cancellous specimens, (2) increased rates of bone formation in femoral diaphyses, (3) increased mass per unit area in both cortical and cancellous bone, (4) less macroradiographic rarefaction of femora and ventebral bodies, and (5) increased ash content of vertebral bodies. These results support the possibility that exogenous calcitonin may be capable of retarding some of the detrimental effects of the adrenal cortical steroids on osseous tissue, especially cancellous bone.

Porcine calcitonin as a renal vasodilator in man.

SUMMARYPorcine calcitonin in intravenous doses of 1, 5, 10 and 20 MRC units produced acute increases in urinary volume and sodium, potassium, chloride and bicarbonate excretion in four normal subjects.Infusion of 10 MRC units over a 30 min period in six normal men produced significant increases in urinary volume and sodium, calcium, magnesium, chloride and urea excretion. Urinary potassium, phosphate and bicarbonate were also increased but the increases were not significantly different from control values.These changes in urinary composition accompanied a significant increase in effective renal plasma flow (para‐amino hippurate clearance) and a smaller increase in inulin clearance.It is suggested that porcine calcitonin acts as a renal vasodilator in man and that changes in renal electrolyte excretion occur as a consequence. It is possible that renal vasodilation is effected by an active intermediary released by calcitonin rather than by the hormone itself.

Effect of porcine, salmon and human calcitonin on urinary excretion of some electrolytes in sheep.

SUMMARY Purified porcine and salmon calcitonin and synthetic salmon and human calcitonin were infused at the rate of 20 MRC mu./kg/h over a 96 h period in intact male lambs. Every calcitonin preparation significantly increased the urinary excretion of inorganic phosphorus, sodium, potassium and calcium, while the urinary excretion of magnesium was always significantly inhibited. Similar significant effects were observed with purified porcine calcitonin in thyroparathyroidectomized lambs supplemented with thyroxine. Oxidation of calcitonin with performic acid completely abolished its effects on plasma calcium and on the kidney. It is concluded that, when used at physiological doses, in sheep calcitonin has an important effect on urinary excretion of inorganic phosphorus, sodium and magnesium.

Hormonal control of the renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol.

Isolated renal tubules from vitamin D-deficient chicks catalyse the in vitro conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol. This conversion is stimulated by 5 x 10(-10) M bovine parathyroid hormone, or by 10(-6) M cyclic AMP. It is inhibited by 10(-9) M porcine calcitonin. It is concluded that these hormonal controls of the synthesis of the renal hormone 1,25-dihydroxycholecalciferol are of particular physiological significance in coordinating the activities of the various organs involved in extracellular calcium homeostasis.

Distribution of thyroid, parathyroid, and ultimobranchial hypocalcemic factors in birds. 1. Thyroid and ultimobranchial calcitonins in pigeons and pullets.

Thyroid glands, parathyroid glands, and “ultimobranchial tissue samples” were dissected separately and identified histologically in pigeons. A rat biological assay for calcitonin was used to measure hypocalcemic activity in these pharyngeal glands of common pigeons, White Carneaux pigeons, and pullets. In the biological assay, log dose—response lines of avian tissue extracts were parallel to that of porcine calcitonin, and hypocalcemic responses of test animals to avian tissue extracts were not abolished by thyroparathyroidectomy. Porcine calcitonin was inactivated by incubation with pigeon and pullet serum; hypocalcemic activity of pullet ultimobranchial extract was reduced by incubation with calcitonininactivating material obtained from rat serum. Pigeon thyroid and ultimobranchial extracts produced hypophosphatemia as well as hypocalcemia in rats. In pullets, hypocalcemic activity was absent from thyroid glands but was present in parathyroid glands, ultimobranchial samples, and cervical nerves. In comm...

Effect of Calcitonin on Parathyroid Hormone-Induced Vasodilation12

The augmentations of hepatic and renal blood flow, induced by parathyroid hormone (PTH) were assessed on anaesthetized dogs. Extracts of porcine and salmon calcitonin as well as the equivalent synthetic calcitonin preparations inhibited the PTH—induced hepatic vasodilation. Salmon calcitonin extract seemed to inhibit the PTH—induced renal vasodilation, but synthetic salmon calcitonin had no such effect. The reason for this discrepancy is not clear. Synthetic human calcitonin up to a dosage of 100 μg/kg did not antagonize die vasodilator action of PTH at all. Calcitonin decreased the maximal augmentation of arterial hepatic flow that could be induced by PTH. This suggests a non—competitive antagonism. (Endocrinology 91: 828, 1972

Vitamin D intoxication treated with porcine calcitonin.

Porcine calcitonin was used to treat three patients with hypercalcaemia due to vitamin D intoxication. In two patients a rapid and sustained fall to normal in serum calcium occurred within three days, in the third patient normocalcaemia was achieved in seven days. In view of its rapid and sustained effect calcitonin may be of value in the urgent treatment of hypercalcaemia due to vitamin D intoxication.

Calcitonin clearance in the pig and in the isolated perfused pig liver.

SUMMARY The metabolic clearance rate (MCR) of porcine calcitonin in six gilts was 13·0 ± 0·7 (s.e.m.) ml/min/kg and in four isolated, perfused pig livers was 16·1 ± 1·1 ml/min, with constant infusions of porcine calcitonin and measurement of calcitonin concentration by radioimmunoassay. After single injections of 125I-labelled porcine calcitonin, the MCR of 125I-labelled porcine calcitonin was 29·2 ± 2·8 ml/min in six isolated, perfused pig livers. 125I-labelled salmon calcitonin was cleared at a slower rate than porcine calcitonin after single injections into the gilt. 125I-Labelled human calcitonin and 125I-labelled salmon calcitonin were not significantly cleared by the isolated, perfused pig liver.

Metabolism of porcine, human and salmon calcitonin in the rat.

SUMMARY Whereas the liver is the major site of accumulation of 125I-labelled porcine calcitonin soon after injection in the rat, both human and salmon calcitonin were rapidly taken up in rat kidney, with relatively insignificant amounts found in the liver. In-vitro studies of degradation of 125I-labelled calcitonins showed that human calcitonin was readily degraded by most rat tissues but the major activity was found in a kidney microsomal fraction, whereas the liver supernatant was most active towards pig calcitonin. Salmon calcitonin was resistant to breakdown by all tissues and fractions except the kidney microsomal fraction, which rapidly degraded it to trichloroacetic acid-soluble fragments. Liver homogenates from a number of mammalian and non-mammalian species degraded pig calcitonin but had little effect on salmon calcitonin. The results show that the kidney is the most important organ in the metabolism of human and salmon calcitonin in the rat, while confirming that the liver is mainly responsible for the metabolism of porcine calcitonin.

Inactivation of calcitonin by specific organs.

THE greater biological potency of salmon calcitonin (SCT) as compared with mammalian calcitonins may be due to the relative resistance of SCT to inactivation in vivo1,2. SCT infused into dogs disappears from the circulation more slowly than does porcine calcitonin (PCT) or human calcitonin (HCT)1–3. For example, the metabolic clearance rate (MCR) of PCT in the dog is approximately 10 times greater than that of SCT1,2. Neither renal excretion3,4 nor inactivation by plasma1,2 is sufficient to account for the rapid clearance of the calcitonins that we have observed in vivo and thus it seemed likely that inactivation of the hormones must occur during passage through one or more organs. Here we present data that suggest the kidney, the liver and muscle and/or bone as the sites of inactivation of the calcitonins in the dog. SCT is relatively resistant to inactivation in the latter two sites.

The acute and prolonged effect of porcine calcitonin on urine electrolyte excretion in intact and parathyroidectomized rats.

ABSTRACT The effect of calcitonin on the urinary excretion of calcium, magnesium, phosphorus, sodium, potassium, and creatinine was studied in intact and parathyroidectomized (PTX) rats. A single injection of porcine calcitonin was followed by a reduced excretion of calcium and magnesium and an increased excretion of potassium. A phosphaturic effect was observed only in the intact rats. The urinary changes did not depend upon impurities in the preparation used, since similar results were obtained with synthetic porcine calcitonin. The urinary electrolyte excretion was also followed in rats given injections of porcine calcitonin every 3 hours, for 3 days. A marked calciuric effect of the hormone was seen in the intact rats, after a transitory decrease in the excretion of calcium at the start of the treatment. The hypercalciuria could hardly be explained by an increased parathyroid action, but rather by a direct effect of calcitonin on renal tubular function. The excretion of magnesium closely followed that of calcium in both intact and PTX rats. A marked phosphaturic and natriuretic effect of calcitonin was observed during prolonged treatment with the hormone. The changes in serum calcium were followed in intact rats treated in a similar way with repeated injections of calcitonin. A hypercalcaemic peak was seen, when the treatment was interrupted, indicating an increased parathyroid action.

Changes of bone cells in calcitonin treated rats.

Rats, age 4 weeks, were treated twice a day with 50 mU MRC porcine Calcitonin s.c. 12, 24, 48 hrs, 1, 2, 3 and 4 weeks after starting the injections, the animals were killed and the epiphysis and metaphysis of the tibia examined

The influence of calcitonins on the disappearance of radiocalcium and radiophosphorus from plasma.

The early temporal (0–2 hr) effects of porcine thyrocalcitonin and salmon ultimobranchial calcitonin were studied in intact rats administered both 45Ca and 32P either 2 weeks before (long-range label) or S min after (shortrange label) sc injection of hormone. Effects of calcitonins on plasma calcium, 45Ca and SA were similar to those reported previously by numerous workers and thereby could be explained by the concept that these hormones act primarily by inhibiting entry of calcium into the plasma. A minor increase in the rate of calcium exit from plasma, has been reported previously, and was also observed in the present study. Effects of calcitonins on 32P were in marked contrast to those on 45Ca. By 20 min after hormone administration, concentrations of both phosphate and 32P in plasma were significantly lower than in control animals and by 1 hr, reached levels 25% less than those in controls. The same results occurred in both short- and long-range experiments. Since both plasma phosphate and 32P fell c...

Effects of porcine calcitonin in osteogenesis imperfecta tarda

The effect of the administration of porcine calcitonin to two children with osteogenesis imperfecta tarda was evaluated by means of calcium and phosphorus balance studies, urinary hydroxyproline excretion, tubular reabsorption of phosphorus, and phosphate clearance before and after administration of parathyroid extract. The balance studies indicated that calcitonin was effective in causing retention of calcium and phosphorus and decrease in hydroxyproline excretion. These improvements suggest that calcitonin may be of therapeutic value in osteogenesis imperfecta by decreasing bone resorption.

Effect of calcitonin on rabbit thyroid glands.

Long-term im administration of porcine calcitonin to rabbits in large doses (100 MRC U/kg body weight as total dose) induces a striking proliferation of thyroid cells. Clusters of interfollicular cells disrupting the follicular pattern and predominance of small follicles lined by high columnar cells with infoldings are evident. Ultrastructurally, most of the thyroid follicular cells are in an apparent hypersecretory state, showing an increase in number and size of microvilli, colloid droplets and heterogeneous dense granules as well as a hypertrophy of Golgi complex. A hyperplasia and hypertrophy of parafollicular (C) cells are also observed. These cells display a large population of small dense granules, free ribosomes and secretory vesicles. These findings suggest that chronic calcitonin administration exerts a goitrogenic effect on rabbit thyroids and also inhibits the release of calcitonin from the parafollicular cells. (Endocrinology 90: 1046, 1972)

Long-term administration of calcitonin for hypercalcemia secondary to recurrent parathyroid carcinoma

A patient with hypercalcemia secondary to recurrent parathyroid carcinoma was treated for 44 days with intramuscular and intravenous injections of porcine calcitonin and on day 45 with synthetic salmon calcitonin. There was no sustained control of serum calcium during this period, but the concentration decreased transiently with intravenous administration of both types of calcitonin. No serial measurements of serum calcium were made following intramuscular administration; therefore, it is not known whether this route of administration produced similar results. Dosage and route of administration of calcitonin warrant further investigation in controlling hypercalcemia secondary to parathyroid hormone excess. No difference in the degree or duration of decreasing the serum calcium concentration was noted following comparable doses of intravenous infusions of porcine calcitonin and of synthetic salmon calcitonin on separate days. Parathyroid hormone levels measured during the infusion of synthetic salmon calcitonin remained elevated at essentially the same level before and after the infusion. A steady decline in urinary phosphorous excretion during the treatment period could not be explained with certainty.

REHYDRATION AS A DIAGNOSTIC AND THERAPEUTIC MEASURE IN HYPERCALCEMIA

Abstract Two patients in a hypercalcemic crisis received fluid replacement therapy, which sufficed to control their condition. Both of them developed a marked polyuria even before they were clinically rehydrated and large amounts of calcium were demonstrated in the urine. A third patient, who clinically presented with the most pronounced symptoms of hypercalcemia, did not produce polyuria or hypercalciuria when rehydrated. It is suggested that the presence or absence of polyuria upon rehydration may serve to distinguish between hypercalcemic crisis sensu strictu and hypercalcemia with less rapid calcium mobilization. When the two first mentioned patients had been brought into a steady state with a stable, but elevated serum calcium and a constant, but abnormally high daily excretion of calcium in the urine, porcine calcitonin was administered. One patient responded with a drop in serum calcium and phosphaturia, both parameters reverting to pretreatment values upon cessation of the drug. In the other patient serum calcium was abruptly normalized, urinary excretion diminished and the effect was sustained.

Calcitonin in the treatment of hypercalcaemic crisis.

Abstract The hypocalcaemic effect of synthetic porcine calcitonin in hypercalcaemic crisis has been studied in a 49‐year‐old man suffering from hypernephroma with skeletal metastases and a 10‐year‐old boy with a primary hyperparathyroidism. In both patients calcitonin induced prompt reduction of serum calcium concentration and pronounced clinical amelioration. This made possible successful removal of a parathyroid adenoma in the young boy. No undesirable side‐effects were observed during treatment with calcitonin.

THE RENAL EFFECT OF CALCITONIN IN HYPOPARATHYROID PATIENTS

AbstractTo rule out secondary effects due to stimulation of the parathyroid glands, the action of calcitonin has been studied in four hypoparathyroid subjects. The patients were given a single injection of 100 MRC U of porcine calcitonin. Apart from a transient decrease in the serum calcium levels in two of the patients, no changes were found in the blood. Pronounced alterations, however, took place in the urinary excretion patterns. The excretion of calcium, magnesium, sodium and potassium increased in all patients. A strong phosphaturic effect was registered in three of the patients. The most prominent changes took place in the excretion of sodium, which went up by 350–700%, accompanied by marked elevations of the diureses. The results indicate that calcitonin has an action on the kidney in man.