The effects of fasting and refeeding on serum parathormone and calcitonin concentrations in young and old male rats.

Although fasting and refeeding reveal the existence of age-related changes in carbohydrate and lipid metabolism, the effects of aging on mineral metabolism in refed animals are unknown. We therefore investigated hormonal regulation of calcium metabolism in young (4 months) and old (26 months) male rats fasted for 48 hours and then refed for 4 or 24 hours. Serum concentrations of total and ionized calcium and parathormone were similar in control young and old rats. Serum calcitonin level was higher, and the concentrations of albumin and inorganic phosphate and alkaline phosphatase activity were lower in fed old rats. In young fasted rats, the serum ionized and total calcium was decreased, and phosphate concentration was increased. In old rats, fasting resulted in the increase of serum parathormone level. Fasting reduced serum alkaline phosphatase activity to a similar extent in both age groups. In young rats, refeeding for 24h normalized serum calcium and phosphate levels and alkaline phosphatase activity, and decreased serum concentrations of PTH and calcitonin. In old refed rats, serum calcitonin concentration was raised by 77% compared to fed or fasted animals, whereas parathormone levels were normalized. Our results indicate that old fasted or refed rats maintain normal serum calcium concentration in a different way than young animals, possibly through the increase in serum levels of parathormone and/or calcitonin. Thus, dietary manipulations such as fasting and refeeding constitute an interesting model for the investigation of the effects of aging on the hormonal regulation of serum calcium level.     

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.     

Immunofluorescent localization of calcitonin in the ultimobranchial gland of Rana temporaria and Rana pipiens

Summary Calcitonin-like immunoreactivity has been demonstrated by immunofluorescence in the cells of the ultimobranchial gland of two species of Rana, using an indirect (sandwich) technique with anti-pure porcine calcitonin serum. The possibility of cross-reactivity, between the amphibian hormone and anti-porcine calcitonin antibody, had been anticipated on account of the observation that injected porcine calcitonin lowered the plasma calcium levels in one of the species under investigation.     

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.

     

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.     

Effects of salmon calcitonin and anti-salmon calcitonin antibody on plasma calcium concentrations in the goldfish,Carassius auratus

The role of calcitonin (CT) in plasma calcium regulation was studied by the administration of exogenous CT and anti-salmon(s) CT antibody using goldfish,Carasius auratus, loaded or otherwise with calcium. CT elicited a decrease in plasma calcium concentrations at a dose of 10 ng/g body weight 1 h after administration. However, no effects were observed following doses of 30 ng and 50 ng/g 1 h, nor for the three doses 3 h after administration. In calcium-loaded fish, the effect of CT was different depending on the dosage of CT. Ten ng and 50 ng/g induced a decrease and an increase in plasma calcium concentrations, respectively, 3 h after administration. Anti-sCT antibody (0.02 μg or 0.1 μg/g) did not affect plasma calcium concentrations. In calcium-loaded fish, neither dose of anti-sCT antibody changed plasma calcium concentrations 1 h after administration. However, following a dose of 0.1 μg/g, plasma calcium concentrations decreased after 3 h. A positive correlation between plasma calcium concentrations and the gonad somatic index (GSI) in females was no longer apparent after administration of anti-sCT antibody. There was no relationship between plasma calcium concentrations and GSI in control and anti-sCT antibody-treated males. These results suggested that CT regulates plasma calcium concentrations in different ways depending on the dosage with CT having a role in calcium physiology during vitellogenesis.     

Calcium metabolism in essential hypertension: relationship to altered renin system activity

Hypertensive disease is associated with various abnormalities of calcium metabolism although how these abnormalities relate to the elevated pressure remains unclear. Based on the use of renin-sodium profiling, we have defined heterogeneous deviations in circulating levels of ionized calcium and magnesium as well as of the calcium-regulating hormones parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D (1,25D), which parallel similar deviations in plasma renin activity. Essential hypertensive subjects with a profile of low renin, lower ionized calcium, and elevated 1,25D respond best to the calcium channel blocker nifedipine, demonstrate an enhanced sensitivity to the blood pressure effects of dietary salt loading, and have significantly lower blood pressures in response to oral calcium supplementation. Hypertensive subjects with the opposite metabolic profile--higher renin activity, higher serum ionized calcium, and lower 1,25D levels--are relatively insensitive to the blood pressure effects of either dietary salt loading or nifedipine, and show no significant hypotensive response to calcium supplements. Altogether, these alterations of calcium ionic and hormonal metabolism suggest that the hormonal control of calcium metabolism is linked to renin system activity as well as to the pathophysiology of the hypertensive process.     

Basal and stimulated calcitonin secretion in primary hyperparathyroidism before and after parathyroidectomy

To investigate calcitonin secretion in primary hyperparathyroidism, basal and stimulated (3 mg Ca++/kg body weight/10 min) immunoreactive calcitonin plasma levels were studied before parathyroidectomy. Plasma calcitonin levels were raised in 50% of patients regardless of sex, but a significant correlation between basal plasma calcium and calcitonin was found only in males. A reduced calcitonin response to calcium infusion was observed in all patients. Parathyroidectomy invariably induced a normalization of calcitonin basal levels. Our findings confirm the existence of a decreased parafollicular cell reserve probably as a consequence of the persistent hypercalcemic state in hyperparathyroid patients and suggest that it is more frequent in females.     

Annular nucleolus in Leydig cells of mouse

Summary Parathyroid glands of winter frogs (Rana pipiens) were compared by light and electron microscopy with those of winter frogs homoimplanted with pituitary glands. Serum calcium levels of untreated and pituitary-implanted animals were compared also. Forty-eight hours after pituitary implantation, serum calcium is elevated from a mean winter value of 6.2 mg % to 9.3 mg % and, morphologically, the parathyroid gland appears to be stimulated with respect to secretory activity. Compared with parathyroids of untreated winter frogs, intercellular spaces are diminished after pituitary implantation and glandular parenchyma is composed of cells with closely apposed plasma membranes thrown into interdigitating folds. Dense core vesicles are present in the cytoplasm and, together with microtubules, are encountered near plasma membranes. Golgi lamellae contain electron dense material and exhibit budding of dense core vesicles. Neither myelinated multivesicular bodies, presumably cytolysosomes degrading unneeded parathormone and organelles, nor focal dilatations with myelination of Golgi lamellae are encountered in parathyroid cells of pituitary implanted frogs. Rough endoplasmic reticulum and mitochondria do not undergo marked changes in distribution or abundance after pituitary implantation, indicating that the synthetic aspects of the secretory process are little altered in untreated and treated animals. It is suggested that in addition to Ca⁺⁺ a pituitary factor is involved in the seasonal changes in amphibian parathyroid structure and function.The authors wishes to thank Mrs. Mary Lee, Mr. Johnny Sandifer and Mr. M. G. Barker for expert technical assistance. This work was supported by the 1972 South Carolina State Appropriation for Research.     

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.     

The effect of porcine calcitonin on plasma calcium in Channa punctatm Bloch

The effect of porcine calcitonin on the plasma calcium of the freshwater Indian murrel, Channa punctatus Bloch has been studied. An injection of 200 MRC mU of porcine calcitonin was given intraperitoneally, while control fish received the gelatin carrier. A significant hypocalcaemia was noted I h after calcitonin treatment (P < 0.001). The plasma calcium had returned to the normal level by the 6th h.     

Some Complicating Factors in the Study of the Calcium Metabolism of Teleosts

A number of factors which may complicate studies dealing withthe calcium metabolism of teleosts are pointed out. Thus, lowenvironmental levels of calcium markedly affect both gill RNAand sodium metabolism in dilute sea water, and the absence ofmonovalent cations affects calcium metabolism in dilute environments.Hypophysectomy is not always followed by the disappearance ofcortisol from the plasma, and prolactin—which is requiredfor the survival of either hypophysectomized or intact animalsin a divalent ion-free environment—stimulates cortisolproduction. It is also pointed out that Fundulus kansae can be maintainedin divalent ion-free environments for long periods, and thatcalcium is mobilized from internal reservoirs such as acellularbone and scales. Failure to survive in such environments isdue to the regulatory effect of environmental calcium on sodiummetabolism rather than on calcium metabolism per se. Finally,it is pointed out that while one parameter of calcium metabolism—suchas plasma calcium levels in male fish—may remain constantthroughtout the year, other parameters such as calcium uptakemay vary considerably. Seasonal differencees in responses tomammalian calcitonin have also been noted.     

Calcium rather than calcitonin is dominant to mediate gastric emptying in thyroidectomized rats

Both calcium and calcitonin are important in mediating gastrointestinal motility. Present study tried to study what was the dominant role of calcitonin or calcium replacement on the gastric emptying in thyroidectomized animals. Adult Sprague-Dawley male rats received thyroidectomy or sham operation and then housed for two weeks until motility study, which was conducted using radiochromium to measure gastric emptying. Before motility study these rats were i.p. injected with saline or human calcitonin in the doses of 0.1, 1 and 10 microgM/kg, respectively. Another group of thyroidectomized rats received i.v. infusion of saline or CaCl2 for 30 min before motility study. Among thyroidectomized rats, neither saline nor various doses of calcitonin treatment disturbed gastric emptying compared to this of sham operated rats. Thyroidectomy diminished plasma calcium level, however, additional calcitonin treatment did not restore the suppressed calcium level (P<0.01). Of rats following saline or CaCl2 infusion, thyroidectomy did not change gastric emptying, whereas CaCl2 infusion enhanced gastric emptying (P<0.05). In conclusion, exogenous calcium treatment further enhances gastric emptying in thyroidectomized rats, whereas calcitonin replacement has no effect on gastric emptying. We suggest that calcium rather than calcitonin is dominant to mediate gastric emptying.     

The effect of thyroparathyroidectomy, parathyroid hormone and calcitonin on plasma strontium in rats

The effect of thyroparathyroidectomy (TPTX) on the plasmatic Sr concentrations in rats previously supplemented with this element, has been studied, as well as its effect on the treatment of TPTX rats with hormonal combinations and, finally, the one presenting hormonal excess or defect of the phosphocalcium metabolism regulating hormones: parathormone (PTH) and calcitonin (CT). Twenty four hours after TPTX, the plasmatic Sr concentrations show a pattern similar to those of Ca and Mg and contrary to Pi. The subsequent evolution is different, as the plasmatic concentrations increase, probably due to the maintenance of Sr supplementation. The administration of this element to TPTX rats and the treatment with a hormonal combination with two of the following hormones: PTH, CT and T4 antagonize the hormonal effect on the restoration of the plasmatic concentrations of the elements analyzed. The PTH excess and defect (TPTX treated with CT + T4) show plasmatic increases in Sr; the CT excess provokes decreases while the defect (administration of PTH + T4) causes increases. The T4 administration reproduces the CT effects, but inconsistently. These results suggest that CT may be the hormone that plays a regulating role in the plasmatic Sr concentrations.     

Morphological and functional characteristics of human temporal-bone cell cultures

Morphology and calcium metabolism have been studied on five different cell cultures from human normal adult temporal-bone biopsies obtained during five stapedectomies. Control cell cultures were obtained from normal human skin. Four different cell types were observed in the bone biopsies: 1) osteoblast-like cells; 2) osteoclast-like cells; 3) fibroblast-like cells; 4) intermediate cells. However, morphology by itself is inadequate for clear differentiation of the four cell types. Hormonal stimulation with calcitonin and dibutyryl-cAMP in presence of 45Ca++ showed a clear-cut difference in 45Ca++ uptake between cultured cells deriving from bone and skin. Functional responses to hormonal stimulation are therefore more specific than cell shape and morphology in differentiating fibroblasts from bone cells. Since responses to hormonal stimulation confirm that temporal-bone cell cultures actually contain bone cells, such cultures seem to be a good experimental model for the study of bone morphology and physiology.     

Calcitonin—C.N.S. action to control the pattern of intestinal motility in rats

Synthetic calcitonin injected into the lateral ventricles (ICV) of rats at picomolar concentration restores the “fasted” motility pattern of the small intestine in fed rats at doses as low as 0.083 picomoles. This effect which appeared in less than 5 min and persisted at least 2 hours for 0.83 picomole, was blocked by a previous intraventricular administration of 10 μg of calcium gluconate. At 0.83 picomole ICV, calcitonin also suppressed the disruption of the “fasted” pattern induced by intravenous infusion of Pentagastrin (6 μg·kg^?1·h^?1) but not that induced by insulin (0.5 U·kg^?1). These findings support the hypothesis that calcitonin acts centrally to control the pattern of intestinal motility by inhibiting the digestive influences responsible for the “fed” pattern. All of these peripheral influences are mediated by a Ca⁺⁺ sensitive central structure.     

Dent disease: A window into calcium and phosphate transport

This review examines calcium and phosphate transport in the kidney through the lens of the rare X‐linked genetic disorder Dent disease. Dent disease type 1 (DD1) is caused by mutations in the CLCN5 gene encoding ClC‐5, a Cl^?/H⁺ antiporter localized to early endosomes of the proximal tubule (PT). Phenotypic features commonly include low molecular weight proteinuria (LMWP), hypercalciuria, focal global sclerosis and chronic kidney disease; calcium nephrolithiasis, nephrocalcinosis and hypophosphatemic rickets are less commonly observed. Although it is not surprising that abnormal endosomal function and recycling in the PT could result in LMWP, it is less clear how ClC‐5 dysfunction disturbs calcium and phosphate metabolism. It is known that the majority of calcium and phosphate transport occurs in PT cells, and PT endocytosis is essential for calcium and phosphorus reabsorption in this nephron segment. Evidence from ClC‐5 KO models suggests that ClC‐5 mediates parathormone endocytosis from tubular fluid. In addition, ClC‐5 dysfunction alters expression of the sodium/proton exchanger NHE3 on the PT apical surface thus altering transcellular sodium movement and hence paracellular calcium reabsorption. A potential role for NHE3 dysfunction in the DD1 phenotype has never been investigated, either in DD models or in patients with DD1, even though patients with DD1 exhibit renal sodium and potassium wasting, especially when exposed to even a low dose of thiazide diuretic. Thus, insights from the rare disease DD1 may inform possible underlying mechanisms for the phenotype of hypercalciuria and idiopathic calcium stones.     

Clinical use of calcimimetics in the treatment of hyperparathyroidisms

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in the extracellular ionized calcium concentration (Ca(2+)ec) regulates parathormone (PTH) and calcitonin secretion, urinary calcium excretion and ultimately bone turnover. Cloning of CaR and discovery of mutations making the receptor less or more sensitive to calcium allowed a better understanding of several hereditary disorders characterized either by hyperparathyroidism or hypoparathyroidism. CaR became an ideal target for the development of compounds able to modulate the activity of CaR, activators (calcimimetics) as well as inhibitors (calcilytics). The calcimimetics are able to amplify the sensitivity of the CaR to Ca(2+)ec, suppressing PTH levels with a resultant fall in blood Ca2+. They dose-dependently reduce the secretion of PTH in vitro in cultured parathyroid cells, in animal models and in humans. In uremic animals, these compounds prevent parathyroid cell hyperplasia, normalize plasma PTH levels and bone remodelling. In uremic patients undergoing hemodialysis, the calcimimetics reduce plasma PTH concentration at short-term (12 weeks) as well as at long-term (2 years), serum calcium-phosphorus product and bone remodelling. After one year of treatment, these patients show a gain of bone mass of 2-3% at the femoral neck and at the total body. Contrarily, the calcilytics, by inhibiting CaR, can intermittently stimulate the secretion and the serum concentration of PTH. This results in an skeletal anabolic effect with a substantial increase in bone mineral density. They are potentially very interesting for the treatment of post-menopausal osteoporosis.     

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.     

Antibodies against calcium-regulating hormones in infectious-allergic forms of bronchial asthma

Antibodies to calcitonin, parathyroid hormone and cortisol are detected in acute stage of infection-caused bronchial asthma. The appearance of antibodies is paralleled by marked hypercalcaemia. The antibodies may bind excessive hormones in the blood, preventing further hormonal imbalance. Ten-day treatment with glucocorticoids decreased the amount of antibodies possibly due to normalization of hormonal secretion and restoration of their balance. As a result, calcium blood levels returned to normal.