Parathormone Effect

Fig. 10.9 How parathormone raises the free calcium ion concentration of blood plasma. PTH parathormone. Effects of PTH are shown by arrows from left to right and down. Effects of calcitriol are shown by arrows running from right to left and down...

Four small parathyroid glands are embedded on the posterior surface of the thyroid gland as it wraps around the trachea. Parathyroid hormone (PTH, parathormone) is the principal regulator of calcium metabolism. Its overall effects include ... 

The polypeptide parathormone is released from the parathyroid glands when plasma Ca + level falls. It stimulates osteoclasts to increase bone resorption in the kidneys, it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of calcium to precipitate as bone mineral decreases. By stimulating the formation of vit D hormone, parathormone has an indirect effect on the enteral uptake of Ca + and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that unlike parathormone, is effective orally. 

The changes in calvarial phosphatase activities observed in animals treated with 25-(OH)D3 are totally different from those obtained with either 1.25-(OH)2D3 or 24.25—(OH)2D3. This fact indicates that physiological doses of 25-(OH)D3 may have an effect on cellular activity, independent of the conversion of this metabolite into these dihydroxyderivatives. The various effects of these vitamin D3 metabolites cannot be correlated with changes in serum calcium and/or phosphate concentrations. Among those factors other than serum calcium and phosphate concentrations that may be involved in the mechanism of action of vitamin D3 metabolites on bone phosphatase activities, the parathyroid hormone is of importance. This hormone is known to be a potent activator of bone phosphatases223,224,228. Parathormone increases the content of alkaline, neutral and acid phosphatases in mouse calvaria in vitro. Calcitonin does not prevent the increase of those enzymes while dichloromethylene diphosphonate causes a decrease in acid phosphatase and pyrophosphatase226. ... 

All the pharmacological and behavioural effects elicited by dopamine agonists and antagonists in the brain can only be explained if such an interaction occurs at the level of the dopamine receptor (D2 receptor site) the site still remains in search of a function. Bovine parathyroid cells were reported to possess dopamine sites which should be involved in the control of parathormone secretion. However, the very poor pharmacological characterization and the lack of in vivo evidence do not allow to assess the dopaminergic nature of this hormone secretion. Dopamine-sensitive adenylate cyclase is thus not a receptor directly implicated in the dopaminergic neurotransmission it is an enzyme which could have an important role in the control of long term metabolic effects such as the synthesis of neuronal constituents. 

ADTN and other dopamine agonists mimicked this effect which was antagonized by a- and B-flupenthixol, the a-isomer being 100 times more potent. In a similar way, dopamine caused a rapid 20-30-fold increase in cellular cAMP in dispersed bovine parathyroid cells. The potency of a series of dopaminergic agonists and antagonists on adenylate cyclase activity paralleled the effects of these ligands on CAMP accumulation and parathormone secretion (16). It was concluded that bovine parathyroid cells possess dopamine sites which are involved in the control of parathormone secretion. 

Kenny and Heiskell (Kl) regard the phosphaturic effect of thyrocalcitonin as possibly due to secondary stimulation of parathormone release by hypocalcemia this is not, however, supported by the findings of Robinson et al. (R4) and Milhaud and Moukhtar (M9) that the phosphaturic effect of thyrocalcitonin was present in parathyroid-ectomized and thyroparathyroidectomized rats, respectively. It has been... 

The effects of thyrocalcitonin in reducing the serum levels of calcium and phosphate, and in increasing the output of phosphate in the urine, have not at present been shown to be significantly influenced by any hormone other than parathormone. Milhaud ef al. (M8) found that neither the thyrocalcitonin content of the thyroid gland nor the hypo-calcemic activity brought about by administration of thyrocalcitonin was significantly altered by hypophysectomy. The presence or absence of the thyroid gland, and therefore of thyroid hormone, does not appear to influence the sensitivity of an animal to thyrocalcitonin administration, while the interrelationship, if any, to suprarenal cortical activity does not appear to have been studied as yet. 

The known effects of thyrocalcitonin are primarily in bone. Removal of the gut had no effect on the hypocalcemic effect of calcitonin (A6), and neither did nephrectomy (H8). No change in soft tissue calcium content was seen in soft tissues to explain the hypocalcemia (Kl). Calcitonin apparently inhibits bone resorption and thereby decreases calcium entry into the blood. Calcitonin prevents the release of calcium from cultured bone (A5, FIO). In vivo, the release of Ca from prelabeled bone is decreased by calcitonin (Jl). The bone arteriovenous difference in calcium levels is increased by calcitonin (M3). The mode of action of calcitonin is unknown. Calcitonin does not inhibit parathormone (A6, H7, T3), nor is its effect apparently mediated through RNA synthesis (T3). 

Jaffe HL, Bodansky A, Blair JE. 1932. The effects of parathormone and ammonium chloride on the bones of rabbits. J Exp Med 55 695-701. 

Later, Cordova et al. (1990) studied the regulating hormones of Ca and the effects of the administration of parathormone (PTH) and CT in rats and after thyrop>arathyroidectomy (TPTX) were analyzed. The PTH excess and defect (TPTX treated with CT + T4) showed plasmatic increases in Sr. However, CT excess provokes decreases while the defect (administration of PTH + T4 to TPTX rats) causes increases. Consequently, CT may be the hormone that plays a regulating role in the plasmatic Sr concentrations. 

Hypomagnesemia is caused by reduced oral or intestinal intake (magnesium-poor diet, malabsorption, alcohol abuse), increased gastrointestinal or renal excretion, hormonal effects (sexual and thyroid hormones, parathormone), and water and electrolyte imbalance. 

Control of Parathormone Secretion 347 Effect of Parathormone Hyperparathyroidism 350... 

Low levels of plasma phosphate stimulate the conversion of the 25-hydroxyl derivative to the 1,25-hy-droxyl compound, while high levels of plasma phosphate enhance the formation of the 24,25-hydroxylated derivative. The mobilization of calcium from bone seems to require both parathormone and the 1,25-hydroxylated derivative. An effect of calcitonin on... 

If vitamin D has no effect on calcium absorption, it does affect calcium mobilization and thereby restores plasma concentrations of calcium. This finding explains why vitamin D deficiency was associated with hypocalcemia. The effect on the bone seems to require a synergetic action of vitamin D and parathormone. The 1,25-hydroxylated derivative seems to be the major active compound causing calcium release from the bone. The 25-hydroxyl derivative has, however, been shown to be active as well. Finally, vitamin D increases renal proximal tubular reabsorption of phosphate in normal and vitamin D deficient animals. Consequently phosphate excretion is decreased. Inasmuch as this effect occurs in parathyroidectomized animals, the effect of vitamin D or its metabolites must be direct. Again, the active metabolites are the 25 and 1,25-hydroxy derivatives. A calcium binding protein has been isolated from the kidney cortex, but its role in renal reabsorption is not known. 

A peritoneal lavage technique was developed which permitted study of the effect of calcium and phosphate on the parathyroid. Parathyroid activity is measured by counting the development of osteoblasts in bone. Using calcium-free and phosphate-free lavage, investigators established that the calcium levels of serum control parathyroid secretion directly, and that any effect of the phosphate is indirect on parathormone secretion. 

The major effect of parathormone is to maintain the calcium levels of serum constant by acting on at least three target organs bone, kidney, and the barrier between the plasma and extracellular fluid. It is now generally accepted that parathormone primary affects bone. 

Although an effect of parathormone on the calcium reserves of bone can no longer be contested, the metabolic mechanism that triggers the demineralization or the site of action of the hormone in the bone remains... 

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