Stimulate Calcitonin Secretion Research Articles

A method for the evaluation of calcitonin secretion using the isolated perfused porcine thyroid

A method for the in vitro perfusion of isolated porcine thyroid glands was developed. The intact glands were placed in a chamber and perfused at a rate of 2.5 ml/min with an oxygenated Tris-balanced salt solution maintained at 37°C. Perfusate fractions were collected at 5-min intervals and analyzed for immunoreactive porcine calcitonin (CT). Calcitonin secretion increased in a dose-related manner with the level of calcium ion (2.5–6.25 mM) in the perfusion solution to a level of 7.5-fold greater than baseline levels. Other established CT secretagogues, such as theophylline (5 mM) and pentagastrin (4 μM), were found to stimulate calcitonin secretion. The CT secretory responsiveness of this system appears to mimic, both quantitatively and qualitatively, the secretory pattern observed in vivo in the pig. Therefore, this perfusion method should provide a valid in vitro model for the study of the process of CT secretion in the mammalian thyroid.

Somatostatin and calcitonin release from perfused dog thyroid lobes. Studies with calcium and pentagastrin.

The C-cells of the thyroid contain and secrete at least two hormones, calcitonin and SRIF. In the present study we have investigated the possible relationship and interdependence of calcitonin and SRIF secretion from perfused dog thyroid lobes. Increases in perfusate Ca++ induced pronounced secretion of both SRIF-like immunoreactivity and of calcitonin-like immunoreactivity. However, the secretory patterns were not identical. The release of calcitonin-like immunoreactivity was more sensitive to small increases in Ca++ than that of SRIF-like immunoreactivity and the shapes of the release curves of calcitonin and SRIF during a 14-min Ca++ infusion were different. Pentagastrin induced only modest increases in SRIF release. The calcitonin response to pentagastrin was characterized by an initial increase followed by a rapid return to near basal levels. This observation was very different from Ca++-induced calcitonin release. Exogenous SRIF infused during pentagastrin or Ca++ stimulation of calcitonin secretion had only a marginal inhibitory effect. The studies indicate that the dynamics of release of various C-cell substances are different when challenged by the same stimulant, and that different stimulants induce different types of variations in the release of the same substance.

Influence of VIP on thyroid hormone secretion

Since VIP occurs in intrathyroidal nerves its role in thyroid hormone secretion has been investigated. It has been found that VIP is a stimulator of iodothyronine secretion in mice. In this respect VIP has a weaker potency than TSH, but shows a similar time characteristic. Also, VIP and TSH potentiate each others effects. In contrast to the effect of TSH, that of VIP is uninfluenced by α-adrenoceptor blockade. VIP, like TSH, stimulates thyroid cyclic AMP production. Thus, VIP nerves might, together with TSH, adrenergic and cholinergic nerves and other peptides such as somatostatin, participate in the complex regulation of iodothyronine secretion. Beside this, VIP has also been found to stimulate calcitonin secretion in rats. Other intrathyroidal neuropeptides, such as substance P and CCK-4, have been found to be without effects on iodothyronine secretion, but, like VIP, to stimulate calcitonin secretion.

Biogenic amines and the secretion of parathyroid hormone and calcitonin.

I. Introduction Ionic and nonionic control of parathyroid hormone and calcitonin secretion There is general agreement that the plasma concentration of calcium is the dominant regulator of parathyroid hormone (PTH) secretion (1–4) and probably also of calcitonin (CT) release (5, 6). Calcium stimulates CT secretion but inhibits PTH release; hypocalcemia has the opposite effects. Under certain conditions, other divalent cations, especially magnesium, can influence PTH and CT secretion in a fashion parallel to that of calcium, but there is little evidence that these relationships are of importance within the physiological range (3, 4). Normal secretion of PTH does, however, require the presence of magnesium (8, 9). Absence of the chloride and hydroxyl anions impairs PTH release in vitro (10), but it seems unlikely that levels of those anions have a specific regulatory function in calcium homeostasis. Phosphate infusion stimulates PTH secretion only by lowering plasma ionic calcium levels (2, 11), and an early...

The Effects of L-Dopa on inVitroandin VivoCalcitonin Release from Medullary Thyroid Carcinoma*

The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed.

EFFECT OF AN INTRAVENOUS INJECTION OF CHOLECYSTOKININ-PANCREOZYMIN ON PLASMA CALCIUM AND CALCITONIN LEVELS IN NEWBORN LAMBS

I.N.R.A., Theix, 63110 Beaumont and *Laboratoire de Physiologie du Développement, Université Pierre et Marie Curie, 9 quai St Bernard, 75230 Paris Cedex 05, France (Received 19 January 1976) The existence of a gastrointestinal-thyroid 'C' cell axis has been proposed as an integral part of postprandial calcium homeostasis (Care, Bates, Swaminathan & Ganguli, 1971). Gastrin or pentagastrin administration to 3-month-old lambs (30 kg body weight) induces a decrease in plasma calcium concentration which does not occur in thyroidectomized animals (Barlet, 1972). Gastrin injection into 1-h-old fasted newborn lambs fails to decrease and increase respectively plasma calcium and calcitonin (CT) concentrations (Barlet, Michel, Thériez, Savajol & Garel, 1974). Thus gastrin seems effective in stimulating CT secretion after weaning but not before. However, calcium chloride (10 mg Ca/kg body weight) given orally to these newborn lambs triggers an increase of CT secretion 1 h later whereas plasma calcium concentrations remain unchanged (Barlet et al.

THE RELATIONSHIP BETWEEN FOOD, GASTRO-INTESTINAL HORMONES AND CALCITONIN SECRETION

SUMMARY The role of calcitonin (CT) in postprandial calcium homeostasis and the possibility of a gastroentero-thyroid C-cell system was studied in young pigs. When pigs were fasted for more than 36 h and then fed, the plasma calcium concentration decreased by 6·1% over a period of 60–120 min after a meal. Since in thyroidectomized pigs the plasma calcium concentration increased by 7·2% when they were fed after a fast of 36 h it is suggested that increased CT secretion assists in the control of postprandial hypercalcaemia. Direct measurement of CT in peripheral plasma supported this suggestion. Because the plasma calcium concentration in an intact pig on a normal feeding regime does not change after a meal, the possibility of the involvement of one or more humoral factors in the stimulation of thyroid C-cells was investigated. Exogenous gastrin and endogenous gastrin stimulated by meat extract were both previously shown by us to increase CT secretion rate. This observation has now been extended to include other stimuli to endogenous gastrin, e.g. glycine and gastric distension. Furthermore, partially purified enteroglucagon increased CT secretion rate from perfused thyroid glands, isolated in situ. Stimulation of endogenous entero-glucagon by the intraduodenal administration of glucose, and probable stimulation of endogenous pancreozymin by intraduodenal fat, were both associated with an increased CT secretion rate from the thyroid gland. These results support the concept of a gastroentero-thyroid C-cell system which serves to stimulate CT secretion and thus to protect the skeleton from excessive bone resorption during periods of dietary sufficiency.

Relations of calcitonin and gastrin in the Zollinger-Ellison syndrome and medullary carcinoma of the thyroid.

Fasting plasma immunoreactive human calcitonin and fasting serum immunoreactive human gastrin were measured by specific radioimmunoassays in 16 healthy persons, eight patients with the Zollinger-Ellison syndrome who had no clinical thyroid disease, and seven patients with medullary carcinoma of the thyroid. All patients with the Zollinger-Ellison syndrome had high serum immunoreactive gastrin (p < 0.01), and all with thyroid carcinoma had high plasma immunoreactive calcitonin (p < 0.025). Mean plasma immunoreactive calcitonin was increased significantly in patients with the Zollinger-Ellison syndrome (p<0.005). Mean serum immunoreactive gastrin was decreased significantly in the patients with carcinoma(p < 0.01). One patient with the Zollinger-Ellison syndrome and high plasma immunoreactive calcitonin had no post-mortem histologic evidence of medullary carcinoma of the thyroid. These observations suggest a possible interhormonal relation between calcitonin and gastrin in man, calcitonin inhibiting gastrin secretion and, conversely, gastrin stimulating calcitonin secretion.

Calcium and phosphorus metabolism parathyroid hormone, calcitonin and bone histology in pseudohypoparathyroidism.

Abstract. High blood levels of immunreactive parathyroid hormone and normal levels of calcitonin were detected in a 14‐yearoIdgirl suffering from pseudohypoparathyroidism. Antibodies to parathyroid hormone have not been detected. Normalization of the serum calcium concentration suppressed parathyroid hormone and stimulated calcitonin secretion to a reproducible extent. Prolonged administration of parathyroid extract induced an increase ofphosphaturia and subsequently normalized the serum calcium level, while intestinal absorption of calcium did not improve. High values for the exchangeable calcium pool and the bone accretion rate of calcium were found. Histologically the iliac crest bone showed a deficient degree of mineralization and a high osteoclastic activity. Treatment with die hydrotachysterol for over a year did not normalize the respons‐of urinary excretion of phosphate and cyclic AMP to administration of parathyroid extract. The data presented are compatible with a relative resistance of the renal tubules, the bone tissue and probably the gut to parathyroid hormone and with the co‐existence of a moderate degree of osteomalacia and secondary hyperparathyroidism.

The effects of hypermagnesaemia on calcitonin secretion in vivo.

SUMMARY The influence of magnesium on calcitonin (CT) secretion rate has been studied in pigs by perfusion of porcine thyroid glands, isolated in situ, under controlled conditions of flow rate and blood electrolyte composition. At concentrations of 4·4–12·7 mequiv./l, magnesium stimulated CT secretion in the presence of a normal calcium concentration in the perfusate. The maximum effect was reached at a concentration of about 7 mequiv. Mg/l. At higher magnesium concentrations, the secretion rate of CT tended to revert towards that found with concentrations of calcium and magnesium within the normal range. When hypermagnesaemia was superimposed on hypercalcaemia there was a fall in the secretion rate of CT as the Mg: Ca ratio in the perfusing blood plasma approached 1. The stimulatory effect of hypermagnesaemia was usually less than that caused by an equimolar increase in plasma calcium concentration. The results suggest that changes in plasma magnesium concentration probably do not influence CT secretion under normal conditions.

Role of pancreozymin-cholecystokinin and structurally related compounds as calcitonin secretogogues.

Surgically isolated pig thyroid glands were perfused in situ under controlled conditions with blood, or modified Krebs-Ringer bicarbonate buffer, to which individual gastrointestinal hormones or related compounds were added at a constant rate. The thyroid venous effluent was collected quantitatively and the calcitonin (CT) concentration measured by either bioassay or radioimmunoassay so that the CT secretion rate could be calculated. Porcine secretin (50 pM to 145 nM) did not stimulate CT secretion, in contrast to a significant effect with porcine pancreozymin (1.3–25 nM). Stimulation of CT secretion was also produced by the Cterminal octapeptide of pancreozymin (1.8–17 nM), whereas the N-terminal hexapeptide (70 nM) was inactive. This stimulatory action was reduced by mild oxidation. Cerulein (1–14 nM) and pentagastrin (0.5 μM), which share with pancreozymin the same C-terminal tetrapeptide, also stimulated CT release. (Endocrinology 89: 262,1971)

Suppression and stimulation of calcitonin secretion in medullary thyroid carcinoma

The secretion of calcitonin (CT) was studied in five patients with medullary thyroid carcinoma using a recently developed radioimmunoassay. All patients had elevated basal concentrations of plasma CT. Hypercalcemia, induced by calcium infusion in four patients, led to an increase in plasma CT. Hypocalcemia, induced by EDTA infusion in three patients, was followed by a decrease in plasma CT. Glucagon infusion led to an increase in plasma CT in three patients but to a marked decrease of plasma CT in one patient. These findings demonstrate that the secretion of calcitonin by this carcinoma is nonautonomous and can be suppressed as well as stimulated.