Proparathyroid hormone: biosynthesis by human parathyroid adenomas

Biosynthesis of a precursor (proparathyroid hormone) to human parathyroid hormone was demonstrated during incubation of tissue from parathyroid adenomas. The proparathyroid hormone is labeled more rapidly than parathyroid hormone during incubation with amino acids labeled with carbon-14 and is progressively converted to the hormone. Apparent differences in the relative rate of conversion of precursor to hormone found in different tumors suggest that proparathyroid hormone may accumulate in some of the tumors and be secreted into the circulation.     

Evidence for parathyroid failure in magnesium deficiency

Serum immunoreactive parathyroid hormone (IPTH) was low to nondetectable in spite of hypocalcemia in a patient with chronic magnesium deficiency. The administration of magnesium led to parallel increases in serum IPTH, serum calcium, and renal phosphate clearance. These findings support the view that magnesium depletion may result in impaired synthesis or release of parathyroid hormone in man, or both.     

A parathyroid hormone inhibitor in vivo: design and biological evaluation of a hormone analog

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34] bPTH-(7-34)NH2, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.     

A parathyroid hormone-like protein from cultured human keratinocytes

Parathyroid hormone-like factors have been found in extracts of tumors associated with humoral hypercalcemia of malignancy, many of which are of squamous epithelial origin. Cultured, nonmalignant human keratinocytes were examined for the production of similar factors. Keratinocyte-conditioned medium from ten cultures stimulated the production of cyclic adenosine monophosphate in clonally derived rat osteosarcoma cells sensitive to parathyroid hormone. Bovine [Nle8,18, Tyr34]PTH-(3-34)NH2, a competitive inhibitor of parathyroid hormone, stopped the adenylate cyclase production stimulated by keratinocyte-conditioned medium, but antisera to parathyroid hormone had no effect on such adenylate cyclase activity. The active component of keratinocyte-conditioned medium has a molecular weight exceeding that of native parathyroid hormone. These characteristics are shared by the parathyroid hormone receptor agonists associated with humoral hypercalcemia of malignancy, which suggests that normal human keratinocytes may produce a factor related to that produced by malignant tumors associated with humoral hypercalcemia of malignancy.     

A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression

Humoral hypercalcemia of malignancy is a common complication of lung and certain other cancers. The hypercalcemia results from the actions of tumor factors on bone and kidney. We report here the isolation of full-length complementary DNA clones of a putative hypercalcemia factor, and the expression from the cloned DNA of the active protein in mammalian cells. The clones encode a prepro peptide of 36 amino acids and a mature protein of 141 amino acids that has significant homology with parathyroid hormone in the amino-terminal region. This previously unrecognized hormone may be important in normal as well as abnormal calcium metabolism.     

Parathyroid hormone in plasma in adenomatous hyperparathyroidism, uremia, and bronchogenic carcinoma

The concentration of parathyroid hormone (measured by radioimmunoassay) in plasma of patients with severe chronic uremia is frequently much higher than it is in the majority of cases having adenomatous hyperparathyroidism. igher-than-normal concentrations of parathyroid hormone in plasma are found in a significant percentage of unselected patients with bronchogenic carcinoma.     

2-Thiophenecarboxylic acid: inhibitor of bone resorption in tissue culture

In tissue culture 2-thiophenecarboxylic acid inhibited both spontaneous resorption of bone and that induced by parathyroid hormone. Its action was to inhibit calcium transfer out of bone.     

Parathyroid hormone effects in rats treated with diphosphonate

The ability of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP; 40 milligrams per kilogram of body weight per day) to reduce the hypercalcemic effect of parathyroid hormone in thyroparathyroidectomized rats was confirmed. However, treatment with this large dose of EHDP enhanced the hypophosphatemic effect of a low dose of parathyroid hormone (10 international units per100 grams of body weight), apparently by promoting the renal excretion of phosphate. The data suggest that EHDP may have a direct effect on the renal action of parathyroid hormone and, in this way, may also affect vitamin D metabolism by the kidney.     

Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin

Adenyl cyclase from plasma membrane fractions of rat renal cortex or medulla was assayed by measuring conversion of adenosine triphosphate labeled at the alpha-phosphate with (32)P to cyclic 3',5'-adenosine monophosphate labeled with 32P. Parathyroid hormone activated the enzyme primarily in cortex; vasopressin acted primarily in medulla. These experiments support the conclusion that cyclic adenosine monophosphate mediates the action of parathyroid hormone on the kidney and show that parathyroid hormone and vasopressin stimulate adenyl cyclase at anatomically separable areas within the kidney.     

Parathyroid hormone production in vitro by human parathyroid cells transformed by Simian virus 40

Cells froma human parathyroid adenoma were infected with simian virus 40 and maintained through 13 subcultures in monolayer tissue culture. For more than 9 months, these "transformed" cells contimed to produce parathyroid hormone which was identified by radioimmunoassay and density-gradient ultra centrifugation.     

Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue

A survey of rat tissues by RNA analysis, aimed at uncovering the physiological function of the parathyroid hormone-like peptide (PTH-LP) associated with hypercalcemia of malignancy, revealed the presence of a 1.5-kilobase messenger RNA encoding this peptide in lactating mammary glands. PTH-LP messenger RNA is expressed in mammary tissue only during lactation; it appears and disappears rapidly (2 to 4 hours) as a function of the sucking stimulus. The identity of this messenger RNA was confirmed by cloning the rat PTH-LP complementary DNA, which predicts a peptide with strong similarity to the human homolog. Moreover, extracts from lactating mammary tissue stimulated parathyroid hormone-dependent adenylate cyclase. These findings suggest that PTH-LP plays a physiological role in lactation, possibly as a hormone for the mobilization or transfer (or both) of calcium to the milk.     

Parathyroid hormone-related protein of malignancy: active synthetic fragments

Peptides corresponding to the amino-terminal region of the parathyroid hormone-related protein (PTHrP) of humoral hypercalcemia of malignancy were synthesized. A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes. Like parathyroid hormone itself, in which the activity resides in the first 34 residues, PTHrP peptides of less than 30 residues from the amino terminus showed substantially reduced activity. PTHrP(1-34) had only 6% of the potency of bovine PTH(1-34) in promoting bone resorption in vitro. PTHrP(1-34) strongly promoted the excretion of cAMP and phosphorus and reduced the excretion of calcium in the isolated, perfused rat kidney consistent with the symptoms seen in malignant hypercalcemia.     

Serum parathyroid hormone in X-linked hypophosphatemia

Serum immunoreactive parathyroid hormone(IPTH) is normal in patients with X-linked hypophosphatemic rickets who are not treated with phosphate salts. Phosphate raises IPTH in these patients. Endogenous IPTH does not influence the existing defect in tubular reabsorption of phosphate in male patients.     

Erratum

In the report "Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro," by N. Horiuchi et al. (11 Dec., p. 1566), the caption for figure 1 was inadvertently omitted. The figure is reprinted below with the caption. [See Fig. 1. in Source PDF].     

Bone cells: a serum-free medium supports proliferation in primary culture

Bone-cells isolated from embryonic rat calvaria increase in number two-to threefold when cultured at high, but not at low, population densities in a serum-free medium that contains albumin. Cultured cells respond to parathyroid hormone and exhibit a marked rise in alkaline phosphatase activity during proliferation, which suggests the progressive differentiation or preferential growth of osteoblast-like cells.     

8-Arginine]-vasopressinoic acid: an inhibitor of rabbit kidney adenyl cyclase

Neurohypophyseal hormnones and several synthetic analogs stimulate adenyl cyclase prepared from rabbit kidney medullary tissue. [8-Arginine]-vasopressinoic acid inhibits the stimulation of medullary adenyl cyclase by neurohypophyseal peptides but does not influence the action of parathyroid hormone on adenyl cyclase from kidiney cortex.     

25-Hydroxycholecalciferol: stimulation of bone resorption in tissue culture

25-Hydroxycholecalciferol stimulates release of previously incorporated calcium-45 from fetal rat bones in doses of 0.9 to 27 units per milliliter. This effect cannot be produced by much larger doses of vitamin D(3). Comparison of stimulation of bone resorption by 25-hydroxycholecalciferol and parathyroid hormone reveals similarities with respect to time course, dose-response slope, and inhibition by calcitonin.     

Endotoxin: stimulation of bone resorption in tissue culture

Bacterial endotoxins can stimulate the release of previously incorporated calcium-45 and tritiated proline from fetal rat bone in tissue culture. Endotoxin from Bacteroides melaninogenicus, an organism regularly found in the gingival crevice of man, produces a response similar to parathyroid hormone and is effective at doses as low as 0.1 microgram per milliliter. This response is inhibited by serum and dependent upon the presence of albumin. Endotoxins may play a role in the bone loss characteristic of human periodontal disease.     

成纤维细胞生长因子23与慢性肾病的研究

成纤维细胞生长因子23与人类许多疾病相关,它不仅可以直接调节钙、磷代谢,而且可以间接调节甲状旁腺激素、维生素D代谢。FGF23和klotho蛋白对维持磷酸盐的浓度、血管和骨骼都具有其独特的意义。主要通过与磷酸盐对比,提出了FGF23可以独立预测慢性肾病的不利结果,最后指出FGF23抗体和其C-末端在慢性肾脏疾病的治疗上具有潜力。     

Calcitonin receptors of kidney and bone

Receptors for calcitonin, determined by activation of adenylate cyclase, were found in a distribution among zones of the kidney distinct from that of receptors for parathyroid hormone or vasopressin. Competitive binding studies showed that the receptors for calcitonin are similar in kidney and bone and that their high apparent affinity for salmon calcitonin accounts in part for the high biological potency in vivo of salmon calcitonin.