Disease relevance of PTH

• The effect of PTH on HSP70 mRNA was not mimicked by cAMP analogues, forskolin, phorbol esters, Ca2+ ionophores, or alpha-thrombin; was insensitive to pertussis toxin; and was not due to increased mRNA stability [1].
• In the parathyroid it is present and cosecreted with PTH in response to hypocalcemia [2].
• High doses of vitamin A are known to increase bone resorption through stimulation of lysosomal proteolytic activity, which also leads to increased secretion of PTH [3].
• After PTH infusion the gastrin level both in antral and mixed venous blood increased significantly without inducing systemic hypercalcemia [4].
• Serum PTH values obtained with antiserum C-97 were about 3 times higher in renal failure, 1.75 times higher in normal individuals and those with primary hyperparathyroidism, while similar to values measured with antiserum C-52 in individuals with secondary hyperparathyroidism without renal failure or with pseudohypoparathyroidism [5].

High impact information on PTH

• The rise in alkaline phosphatase activity was specific for T3 since growth-plate cartilage alkaline phosphatase activity was not increased by cortisol, insulin, parathyroid hormone, or 5% fetal calf serum [6].
• To study the mechanism of PTH action, we used AOK-B50 cells, a porcine kidney-cell line with stably transfected opossum PTH receptor in which both the 24-hydroxylase mRNA and activity are down-regulated by PTH [7].
• Because the untranslated regions of genes can determine the stability of its transcripts, we studied the 5' untranslated region and the 3' untranslated region of the rat 24-hydroxylase gene by using reporter-gene strategy to identify possible PTH sites of action [7].
• However, the sites and mechanism whereby PTH causes 24-hydroxylase mRNA degradation are unknown [7].
• However, the mechanism of down-regulation of the 24-hydroxylase by parathyroid hormone (PTH) has not yet been elucidated [7].

Chemical compound and disease context of PTH

• The effect of 1,25-dihydroxycholecalciferol on the parathyroid hormone secretion of porcine parathyroid glands and human parathyroid adenomas in vitro [8].
• Secretion of parathyroid hormone in response to EDTA-induced hypocalcemia in vivo was also less in older rats than in younger ones, giving lower deltaPTH/deltaCa values in the older animal [9].

Biological context of PTH

• Upregulation of 24-hydroxylase by 1,25-dihydroxyvitamin D3 has been characterized; however, the mechanism by which PTH acts to downregulate 24-hydroxylase expression remains unknown [10].
• These studies characterize the regulatory regions of the human 1alpha-OHase gene and provide insight into the physiologic basis for regulation of the expression of this gene by PTH and 1,25(OH)2D3 [11].
• Differences in protein and glycoprotein components, increased membrane fluidity, and responsiveness to PTH indicate that hypertrophic ("ossifying") chondrocytes possess a plasma membrane widely different from that of resting chondrocytes [12].
• PTH elicits multiple second messenger signals in target cells [13].
• These studies demonstrate that bone endothelial cells bear receptors for natriuretic hormones associated with changes in PTH-induced cAMP production, prostaglandin production, and cell proliferation [14].

Anatomical context of PTH

• Here we report the cloning of the porcine 24-hydroxylase, and show that 1,25-dihydroxyvitamin D3-stimulated 24-hydroxylase mRNA and activity are repressed by PTH in AOK-B50 cells, a porcine kidney proximal tubule cell line with stably transfected opossum PTH receptors [10].
• Parathyroid hormone (PTH) activates both adenylate cyclase and phospholipase C in target cells, and cloned PTH/PTH-related protein (PTHrP) receptor can mediate both responses when expressed in host cells such as LLC-PK1 renal epithelial cells [1].
• CgA, in turn, is an acidic glycoprotein of about 450 amino acids that is costored and cosecreted with PTH in the parathyroid gland and with native hormones of many endocrine tissues [15].
• Parathyroid hormone (PTH)/PTH-related peptide receptor density modulates activation of phospholipase C and phosphate transport by PTH in LLC-PK1 cells [16].
• The muscle cells in which cholecystokinin octapeptide and PTH receptors were protected completely abolished the inhibitory responses to VIP and PACAP [17].

Associations of PTH with chemical compounds

• 8. Regulation of HSP70 gene transcription by PTH may be a common cellular response to the hormone, which, in some cells, may not be mediated by activation of adenylate cyclase or protein kinase C [1].
• Increases in serum PTH in this group were not accompanied by increases in calcitriol [18].
• We immunized seven guinea pigs and two goats with the desalted 7.5% TCA supernate (containing about 2% carboxyl-terminal hPTH fragments); three of the guinea pigs and one goat produced high affinity antisera with predominant specificity for the carboxyl-terminal region of PTH [19].
• Bovine PTH (5U/ml equal to 4.2 times 10-7M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, and osteocytes but not in marrow cells [20].
• The stimulatory action of dexamethasone on PTH and CgA mRNA could be noted in 12 h or less and continued through 24-48 h [21].

Regulatory relationships of PTH

• Among its effects on various endocrine glands, pancreastatin strongly inhibits the secretion of PTH and CgA by the parathyroid [15].
• The purpose of this study was to determine whether or not substance P (SP) regulates PTH secretion [22].
• PTH infusion did not significantly influence the somatostatin level either in antral venous blood or in mixed venous blood [4].
• Parathyroid hormone stimulates mammalian renal 25-hydroxyvitamin D3-1 alpha-hydroxylase in vitro [23].

Other interactions of PTH

• The new analogs presented should be useful as minimum-length functional probes of the PTH-PTH receptor interaction mechanism [24].
• It remains to be determined if the changes in transcription of the PTH and CgA genes and stability of their respective mRNAs are direct effects of pancreastatin or secondary actions due to the inhibition of secretion [15].
• In Dex alone treated piglets, PTH was significantly elevated (7-fold), whereas osteocalcin and N-telopeptide were significantly reduced compared with control values [25].
• The muscle cells in which cholecystokinin octapeptide and VIP or PACAP receptors were protected completely abolished the inhibitory response to PTH [17].
• Similar tests on alpha-methyl-D-glucoside uptake showed that serum, TPA, PTH, and AVP had no significant effect on phlorizin-sensitive uptake; however, calcitonin increased uptake by 84% (n = 18) [26].

Analytical, diagnostic and therapeutic context of PTH

• The endocrine response of porcine parathyroid gland tissue slices in vitro to aluminum was studied by electron microscopy and radioimmunoassay of PTH [27].
• All nicotine concentrations and PTH resulted in statistically significantly greater mean percent resorptions than the control group (P < 0.05) [28].
• When circulating PTH taken from patients with these disorders was fractionated by gel chromatography, both antisera recognized similar peaks of intact hPTH(1-84) and of large "C" fragments while antiserum C-97 further recognized a peak of smaller "C" fragments [5].
• Ultrastructural examinations were performed in three groups of pigs; one sham-operated control group, one group subjected to thyroidectomy, and another group injected with parathormone after thyroidectomy (TX + PTH) [29].
• In one experiment the circulatory level of fetal PTH was shown to be higher than in the sow by both an immunoradiometric assay and a very sensitive cytochemical assay [30].

References