Disease relevance of Pth

• These results suggest that osteitis fibrosa caused by advanced s-HPT can be successfully reversed by a control of PTH at an appropriate level through the improvement of PTG hyperplasia as induced by DI-OCT+IV-OCT [1].
• Expression of the gene encoding PTH-related peptide (PTHrP), a protein that plays a primary role in the development of humoral hypercalcemia of malignancy, is down-regulated at the transcriptional level by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] [2].
• DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism [3].
• The parathyroid hormone-induced bone resorption in mouse fetal long bone cultures was inhibited with an IC(50) of 16microg/ml [4].
• Of considerable importance is that these analogs, given to rats at daily doses of up to 70 microg/kg of body weight per day, are either unable or only slightly able to raise serum calcium concentration but are nevertheless able to suppress parathyroid hormone levels in plasma up to 100% and induce 24-hydroxylase mRNA in skin [5].

Psychiatry related information on Pth

• These effects of lithium were not associated with changes in animal behavior, nor were there any significant differences in blood levels of calcium, phosphorus, alkaline phosphatase, creatinine, pH, or parathyroid hormone [6].
• The present study demonstrates that sustained high levels of PTH in the brain might cause degeneration of specific brain regions due to Ca(2+) overloading via activation of dihydropyridine-sensitive Ca(2+) channels, and suggests that PTH may be a risk factor for senile dementia [7].
• Results presented in this paper indicate that intracerebroventricular injection of parathyroid hormone reduces pain threshold in male rats [8].
• Effects of parathyroid hormone on bone formation in a rat model for chronic alcohol abuse [9].
• This study examined the possibility that maternal alcohol consumption may affect fetal bone development by altering fetal levels of parathyroid hormone (PTH), 1,25(OH)2D, or calcitonin (hormones that regulate calcium (Ca) and bone metabolism in the adult animal) [10].

High impact information on Pth

• The major ones, however, are the circulating amounts of parathyroid hormone (the secretion of which is stimulated by low serum calcium), serum or extracellular fluid phosphorus concentrations, circulating levels of 1,25(OH)2D3 itself, and perhaps serum calcium directly [11].
• Parathyroid hormone-responsive adenylate cyclase in induced transplantable osteogenic rat sarcoma [12].
• Parathyroid hormone as a smooth muscle relaxant [13].
• Moreover, extracts from lactating mammary tissue stimulated parathyroid hormone-dependent adenylate cyclase [14].
• 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 [15].

Chemical compound and disease context of Pth

• In summary, we have shown that 19-nor-1,25(OH)2D2, a new analogue of calcitriol is effective in suppressing PTH in uremic rats with secondary hyperparathyroidism [16].
• Mutual up-regulation of thyroid hormone and parathyroid hormone receptors in rat osteoblastic osteosarcoma 17/2.8 cells [17].
• The role of dietary calcium in the physiology of vitamin D toxicity: excess dietary vitamin D3 blunts parathyroid hormone induction of kidney 1-hydroxylase [18].
• However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone [19].
• In bones cultured without PTH, HU decreased the rate of bone resorption, but not the number of osteoclasts per bone [20].

Biological context of Pth

• Although our previous study suggested that Smad3 is an important molecule for the stimulation of bone formation, no reports have been available about the effects of PTH on Smad3 [21].
• PTH fragments added concomitantly prevented the down-regulation seen with 1,25(OH)2D3 [22].
• Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by parathyroid hormone and cAMP-agonists [23].
• The present study demonstrates that PTH and activation of the cAMP signal pathway cause up-regulation of VDR via induction of VDR gene expression [23].
• This indicates that upregulation of CaR mRNA and VDR mRNA is not necessary to induce the rapid normalization of PTH secretion from hyperplastic parathyroid glands [24].

Anatomical context of Pth

• Optimal concentration of 1,25(OH)2D3 (10(-12) M) and of PTH fragments [bPTH(1-34) or hPTH(28-48), 10(-10)M] showed additive effects on DNA synthesis of and colony formation by growth plate chondrocytes [22].
• Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro [22].
• Evidence for coordinated regulation of osteoblast function by 1,25-dihydroxyvitamin D3 and parathyroid hormone [25].
• PTH treatment enhanced the HyA staining of osteocytes in cortical bone tissue sections to the extent that the lacunocanalicular system became visualized [26].
• Finally, it was observed that the lining cells along the endosteal surface of the diaphysis did not stain strongly positive for HyA either naturally or when exposed to PTH treatment [26].

Associations of Pth with chemical compounds

• Incubation for 2 and 4 h with forskolin, Bt2cAMP, PTHrP or prostaglandin E2 caused an increase in the level of VDR mRNA comparable to that caused by PTH [23].
• Inhibition of transcription with actinomycin D (10 micrograms/ml) completely abolished the PTH-induced increase of VDR mRNA and inhibition of translation with cycloheximide (1 microgram/ml) resulted in superinduction of VDR mRNA [23].
• Low extracellular calcium (Ca) stimulates parathyroid hormone (PTH) secretion and also increases the renal synthesis of calcitriol (CTR), which is known to decrease PTH production [27].
• One of these motifs resembles the negative VDRE (nVDRE) from the PTH gene, which is also down-regulated by vitamin D3 [2].
• Plasma urea, creatinine, total calcium, phosphorus, and PTH levels were measured [24].

Physical interactions of Pth

• In this study, the effects of PTH on binding of [3H]-1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and on vitamin D receptor (VDR) mRNA concentration were assessed in intestinal mucosa of subtotally nephrectomized rats (Nx) and in intestinal mucosa of sham-operated rats with normal kidney function (Intact) [28].
• These results show that calreticulin prevents the binding of vitamin D receptor-retinoid X receptor-beta to the PTH VDRE in gel retardation assays and prevents the transcriptional effect of 1,25-(OH)2D3 on the PTH gene [29].
• The minimal PTH-suppressive region (PTHSR) was between +1 and +25 in exon U1, but the 5'-flanking region or Sp1 and MAZ-binding sites also were required for PTH-mediated repression [30].
• Parathyroid hormone (PTH) acts on bone and kidneys by binding to PTH/PTH-related protein (PTHrP) receptors and regulating calcium (Ca) and phosphorus (P) homeostasis [31].
• The effect of transforming growth factor beta1 (TGF-beta1) on the expression of mRNA for the parathyroid hormone receptor and binding of iodinated parathyroid hormone-related protein in ROS 17/2.8 osteosarcoma cells was evaluated [32].

Regulatory relationships of Pth

• Furthermore, PTH enhanced TGF-beta-induced production of type I collagen, whereas it did not affect TGF-beta-reduced proliferation in MC3T3-E1 cells [21].
• We previously reported that PTHrP-induced renal vasodilation is impaired in mature spontaneously hypertensive rats (SHR) through down-regulation of the type 1 PTH/PTHrP receptor (PTH1R), a feature that contributes to the high renal vascular resistance in SHR [33].
• First, mature periosteal osteoblasts, under natural conditions, do not contain much HyA in their surrounding extracellular matrix but dramatically enhance their matrix HyA content when treated with PTH [26].
• Calreticulin inhibits vitamin D's action on the PTH gene in vitro and may prevent vitamin D's effect in vivo in hypocalcemic rats [29].
• The ability of PTH to downregulate renal 24-OHase and the 1,25-dihydroxyvitamin D receptor (VDR) during prolonged Ca restriction remained intact, irrespective of vitamin D status [18].

Other interactions of Pth

• After 24 h the VDR mRNA level in PTH-treated cells returned to control level [23].
• On the other hand, PTH augmented TGF-beta-induced transcriptional activity [21].
• This study investigated whether Rho proteins modulate the PKCalpha translocation and IL-6 promoter activity stimulated by PTH in UMR-106 cells [34].
• To confirm the interaction between PTH1R and both importin alpha(1) and beta, the complex was purified from total cell protein of osteoblast-like cells using a PTH-linked affinity chromatography column [35].
• METHODS: Inhibitory activity against in vitro bone resorption was examined by measuring the Ca2+ release from murine calvariae cultured for 6 days, which were treated with interleukin-1 (IL-1), IL-6, or parathyroid hormone [36].

Analytical, diagnostic and therapeutic context of Pth

• PKCalpha and PKCbetaI are translocated after treatment with PTH in UMR-106 osteoblastic cells; however, the pathway leading to PKC isozyme translocation is not established [34].
• The higher dose of 1,25-(OH)2D3, 6 ng, significantly decreased PTH from 52.7 +/- 10.2 pg/mL in the uremic control group to 25.7 +/- 6.7 pg/mL (P < 0.01) [37].
• A rat tail animal model with computer modeling was used to examine bone response to loading and PTH [38].
• The mRNA for this gene, determined by Northern blotting with a riboprobe for PTH mRNA, was of identical size to the parathyroidal PTH, but its abundance in brain was less than 0.01% of that expressed in the parathyroid glands [39].
• Southern analysis of these PCR and rapid amplification of cDNA end cDNA fragments further indicated homology with PTH cDNA [39].

References