Parathormone

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Hyperparathyroidism Excess parathormone causes bone resorption. 

A nontrophic hormone acts on nonendocrine target tissues. For example, parathormone released from the parathyroid glands acts on bone tissue to stimulate the release of calcium into the blood. Aldosterone released from the cortical region of the adrenal glands acts on the kidney to stimulate the reabsorption of sodium into the blood. 

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 ... 

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

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. 

Parathyrin (parathyroid hormone, parathormone, PTH) is secreted by the parathyroid glands. A peptide of 84 amino acids, it has two precursors during its biosynthesis, a... 

Plasma calcium level is precisely regulated by three hormones e.g. parathormone, calcitonin and calciferol (which is a active form of vitamin D). They control its absorption, exchange with bone and excretion. 

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. ... 

Parathormone) reabsoiption. phosphate excretion, and maintenance of serum calcium... 

Glucocorticoids can even cause osteoporosis when they are used for long-term replacement therapy in the Addison s disease, as has been shown by a study of 91 patients who had taken glucocorticoids for a mean of 10.6 years, in whom bone mineral density was reduced by 32% compared with age-matched controls (SEDA-19, 377 198). However, these results contrasted with the results of a Spanish study in patients with Addison s disease, in which no direct relation was found between replacement therapy and either bone density or biochemical markers of bone turnover of calcium metabolism (alkaline phosphatase, osteocalcin, procollagen I type, parathormone, and 1,25-dihydroxycolecalciferol) (SEDA-19, 377 199). 

Renal calcinosis can develop as a result of hypercalciuria and is a major concern in the treatment of infantile spasms with corticotropin. In 16 infants, corticotropin, often associated with anticonvulsants, results in increased urinary excretion of calcium and phosphate, with increased parathormone serum concentrations and in some cases generalized aminoaciduria (26). This makes it imperative that the dose of corticotropin and the duration of treatment be kept to the minimum required to ensure efficacy. In one case in which calcified stones were removed surgically, recurrence was apparently prevented, despite the presence of a Cushingoid state, by long-term chlorothiazide (27). 

In 70 postmenopausal women with completely resected breast cancers who were disease-free after taking tamoxifen for 2—3 years, a switch to exemestane resulted in increases in serum bone alkaline phosphatase and the carboxy-terminal telopeptide of type I collagen and a fall in parathormone bone mineral density worsened (28). 

A 72-year-old woman received calcitonin 100 IU twice a week intramuscularly, calcitriol 0.25 micrograms bd, and daily calcium supplements for 3 years, before presenting with a raised calcium concentration (2.7 mmol/ 1) and linear calcification in the knee joints. The parathormone concentration was raised (151 pg/ml reference range 7-53) and a parathyroid adenoma was demonstrated on ultrasound (15). 

Most studies of parathormone have involved PTHj 34. In 238 women with post-menopausal osteoporosis randomly assigned to subcutaneous PTHi g4 plus placebo, parathormone plus alendronate, or alendronate plus placebo, there was a significant increase in mean serum uric acid concentrations in those taking parathormone (14). Three women had gout, one in the parathormone-only group and two in the combination group... 

There was hypercalcemia in 12% of 119 patients taking PTH1 g4 100 micrograms/day with daily calcium and vitamin D and in 14% of 59 taking additional alendronate. After stopping the calcium supplements only two women needed a dosage reduction of parathormone (14,17). 

When compared with 12 healthy matched controls, 13 women who had taken lithium for a mean of 8 (range 3-16) years had higher mean ionized and total calcium concentrations, but mean plasma parathormone concentrations did not differ. In eight of the women taking lithium, the calcium concentration was above the upper end of the reference range, and in one the parathormone concentration was abnormally high (661). 

Anecdotal observations suggest that excessive use of oral phosphates may be a risk factor for the development of tertiary hyperparathyroidism in patients with X-linked hypophosphatemic rickets. Of 13 patients with X-linked hypophosphatemic rickets two developed tertiary hyperparathyroidism and 11 secondary hyperparathyroidism during treatment (939). Patients with tertiary hyperparathyroidism had on average earlier and longer treatment and higher doses of phosphates (over lOOmg/kg/day) than the 11 patients with secondary hyperparathyroidism. Those who later developed tertiary hyperparathyroidism had very high serum parathormone concentrations (over 42 pmol/1). 

Sofuoglu S, Basturk M, Tutus A, Karaaslan F, Aslan SS, Gonuk AS. Lithium-induced alterations in parathormone function in patients with bipolar affective disorder. Int J Neuropsychopharmacol 1999 2 S56. 

Rheumatoid arthritis has been reported to be associated with RLS in up to 25 % of cases [43], but serological analysis of 68 RLS patients failed to find association with rheumatological serologies [44], The same holds true for diabetes, often reported in association with RLS however, a recent extensive clinical study did not find a significantly higher prevalence of RLS in diabetic patients [44], Neuropathies associated with rheumatoid arthritis and diabetes may be the cause of RLS in these patients. In patients with end-stage kidney disease, reports showed a mild or overt (from moderate to severe) RLS in up to 62 % of cases [45,46], No correlation with iron levels or other uremia characteristics such as a decrease in parathormone levels has been found [46], Parkinson s disease (PD) has frequently been associated with... 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

Parathormone (protein) Parathyroid Bones Transfer Ca2+ from bone to blood... 

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. 

How the problem arises whether or not the dopamine-sensitive adenylate cyclase (D site) (2) also answers these criteria or other criteria which justify it being called a dopamine receptor like the D2 receptor site 15-8). The purpose of the present paper is to discuss this problem especially with regard to parathormone secretion. Special attention will be paid to the pharmacological characterization of this hormone secretion. 

One may argue that the pharmacology of the site does not necessarily have to be the same as that of the D2 receptor site this is true but the problem is to get an in vivo pharmacology for this site which entirely fits the data obtained in vitro on the cyclase. Up to now there is no answer to this problem. It is generally believed that parathormone... 

In 1977, Brown et al. (15) reported that dopamine (10-8 M) stimulates by 2-4 fold the secretion of parathormone from dispersed bovine parathyroid cells. 

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. 

Compounds which can regulate (+) or not (-) cAMP production and parathormone secretion in parathyroid cells... 

---