The Parathyroid Hormone

For a long time very little progress was made with the purification and isolation of the parathyroid hormone the acid extraction procedure of Collip (Cll) provided the standard commercial extract for over 30 years. 

The introduction of phenol extraction by Aurbach (A4) has enabled Rasmussen (R3) to produce a much more active principle with a potency of about 2500 units (USP)/mg dry weight when assayed by the method of Munson (Mil). This material possesses both phosphaturic and calcium-mobilizing activities. Its minimum molecular weight, calculated from its amino acid composition, is about 8500. Rasmussen interprets his latest 

The purification of the parathyroid hormone represents a major advance which will undoubtedly have repercussions in every aspect of calcium metabolism. 

Parathyroid implantation (B2) and tissue culture experiments (Gl, G2) have shown that the secretion of the parathyroid glands exerts a direct action on bone which results in resorption and destruction. Injection of the hormone produces definite cellular changes within a few hours in the osteoblasts and osteocytes (H3). There is also an increase in the number of osteoclasts. It is impossible to say, however, whether bone mineral or organic matrix is primarily affected, as they appear to be mobilized simultaneously (C6, M5). 

Experimental work has demonstrated the vital role of skeletal mineral in the homeostatic control of blood calcium (H2, C12, T2). The absolute calcium concentration at which homeostasis is preserved is governed, however, by the parathyroid glands. Experimental or accidental parathyroidectomy results in a fall of ionic calcium concentration from about 

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Several years ago, it was discovered that the thyroid gland was also the source of a hypocalcemic hormone having effects in general opposition to those of the parathyroid hormone. This hormone is produced in mammals by the parafollicular C-ceUs and in other vertebrates by the ultimobrachial bodies (45). Originally called thyrocalcitonin, it is now referred to as calcitonin (CT). 

Renal osteodystrophy stems from disruptions in calcium, phosphorus, and vitamin D homeostasis through the interaction with the parathyroid hormone. 

The parathyroid hormone content of blood has not been studied sufficiently to yield any data with regard to variation. The functioning of the glands is so closely related to other factors which regulate calcium and phosphorus metabolism that it is impossible to assign differences in these areas to variation in parathyroid function. The variation of the calcium (and phosphorus) in the blood has been noted (p. 55), and this variation, of course, may be due in a substantial degree to differences in parathyroid functioning. 

The mechanism of G a disease may resnlt from insnfficient parathyroid hormone-related peptide signaling by the parathyroid hormone receptor 1 (PTHRl) in chondrocytes. This deficiency may inhibit the differentiation of chondrocytes within the endochondral growth plate (88,89). A variety of parathyroid hormone abnormalities can result. 

The parathyroid hormone receptor 1 (PTHRl) protein belongs to the GPCR family B. The PTHRl is a receptor for PTH and for parathyroid hormone-related peptide... 

Zhang, P., Jobert, A. S., Couvineau, A., and Silve, C. (1998) Homozygous inactivating mutation in the parathyroid hormone parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. J. Clin. Endocrinol. Metab. 83, 3365-3368. 

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. ... 

Peptide Hormones Peptide hormones may have from 3 to 200 or more amino acid residues. They include the pancreatic hormones insulin, glucagon, and somatostatin, the parathyroid hormone, calcitonin, and all the hormones of the hypothalamus and pituitary (described below). These hormones are synthesized on ribosomes in the form of longer precursor proteins (prohormones),... 

There is antagonism between the parathyroid hormone and glucocorticoids (121). Latent hyperparathyroidism can be unmasked by glucocorticoids (122). 

Whitfield J, Morley P, Willick G. The parathyroid hormone, its fragments and analogues—potent bone-builders for treating osteoporosis. Expert Opin Investig Drugs 2000 9(6) 1293-315. 

Valeur N, Andersen RS. Lithium induceret parathyreoi-deahormon dysfunktion. [Lithium induced dysfunction of the parathyroid hormone.] Ugeskr Laeger 2002 164(5) 639 10. 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

Sheikh, S. P., Vilardarga, J. P., Baranski, T. J., Lichtarge, O., Iiri, T., Meng, E. C., Nissenson, R. A., and Bourne, H. R. (1999). Similar structures and shared switch mechanisms of the beta2-adrenoceptor and the parathyroid hormone receptor. Zn(II) bridges between helices III and VI block activation. J. Biol. Chem. 274, 17033-17041. 

According to Jonxis and Huisman (J6, J9, J12), hyperamino aciduria may be observed among the other members of the family of a patient with common rachitis and may sometimes (but not always) be corrected by vitamin D administration. There are presumably different grades of hereditary vitamin sensitiveness of the renal tubular function to vitamin D. The regulation does not take place through the mediation of the parathyroid hormone. 

The major function of the parathyroid hormone (PTH parathormone) is to regulate the concentration of extracellular calcium. PTH is heterogeneous and circulates as an intact polypeptide and as fragments. The major circulating biologically active peptide is intact PTH, which is rapidly cleared from the circulation (half-life less than 10 min). The N-terminal portion is responsible for its biologic activity. 

Calcium is essential for the normal growth and development of the body, especially (in the form of calcium phosphate) of the bones and teeth. Its level in the blood is regulated by the opposing actions of the thyroid hormone calcitonin, and the parathyroid hormone parathormone. Its uptake from food is enhanced by vitamin D (calciferol). Forms of calcium used therapeutically include the folinic acid supplement calcium foiinate, and the mineral supplements calcium bicarbonate, calcium carbonate, calcium gluconate and calcium lactate. 

The parathyroid hormone (PTH), calcitonin, and vitamin D regulate calcium. 

Strewler GJ. The parathyroid hormone-related protein. Endocrinol Metab Cfin North Am 2000 29 629-45. 

Hoogendam J, Farih-Sips H, Wynaendts LC et al (2007) Novel mutations in the parathyroid hormone (PTH)/PTH-related peptide receptor type 1 causing Blomstrand osteo-chondrodysplasia types I and II. J Clin Endocrinol Metab 92 1088-1095... 

Osteoblasts and kidney cells respond to PTH by possessing a single receptor known as the Parathyroid hormone/Parathyroid hormone-Related protein receptor (PPR). The PTH-mediated activation of the osteoblast PPR receptor reduces OCIF (osteoprotegerin)... 

A second member of the parathyroid hormone family, parathyroid hormone-related protein (PTHrP), is quite similar to PTH in amino acid sequence and protein structure. Like PTH, it activates the parathyroid hormone receptor causing increased bone resorption and renal tubular calcium reabsorption. Increased serum concentrations of parathyroid hormone-related protein are the predominant cause of hypercalcemia in cancer patients with solid tumors. This observation led to its discovery and to the elucidation of its many cellular functions in normal tissues. In contrast to PTH, which is expressed only in parathyroid glands, PTHrP is detected in many tissues in fetuses and adults it is found in epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. This protein is also the principal regulator of placental calcium transport to the fetus. 

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