Disease relevance of PTH

• The nucleotide sequence of avian (chicken) prepro-PTH (prepro-PTH) mRNA was determined from a 2.3-kilobase fragment of complementary chicken parathyroid DNA cloned in E. coli MM 924 [1].
• But after 15 d of vitamin D deprivation, and the supervention of hypocalcemia, 1 alpha-hydroxylase activity was not further increased by the administration of PTH [2].
• The pertussis toxin-sensitive G proteins are involved in the PTH heterologous rather than homologous desensitization of the cAMP response [3].
• Polyacrylamide gel isoelectric focusing after preparation of the enzyme showed a picture similar to that seen after parathyroid hormone (PTH) administration in chicks; therefore, this could be considered a secondary hyperparathyroidism [4].
• Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression [5].

Psychiatry related information on PTH

• These oscillations, triggered by the perturbation imposed by growth, are the result of the dual action of parathyroid hormone on bone on the one hand and on intestinal calcium absorption via the 1,25-dihydroxycholecalciferol synthesizing system on the other and the difference in the response time between the two subsystems [6].

High impact information on PTH

• Vitamin D3 metabolites and PTH synergistically stimulate bone formation of chick embryonic femur in vitro [7].
• To clarify the factors stimulating bone formation or accelerating osteogenic cell activity, we have examined the effects of vitamin D3 metabolites and PTH on bone formation in vitro [7].
• The effect of PTH on chondrocyte proliferation as a function of cartilage age was examined [8].
• PTH also increased [35S]sulfate incorporation into proteoglycans and the cyclic AMP level in fetal and postnatal chondrocytes, but at 100-fold higher concentrations (10(-8)-10(-7) M) than those (10(-10)-10(-9) M) required for the stimulation of cell division [8].
• This age dependency was observed only with PTH: fibroblast growth factor, epidermal growth factor, and insulin stimulated chondrocyte proliferation irrespective of cartilage age [8].

Chemical compound and disease context of PTH

• Modulation of responsiveness of the adenylate cyclase system in avian chondroprogenitor cells by pertussis toxin, PTH, and PGE2 [3].
• PTH homologous desensitization was not affected by pertussis toxin treatment, but the heterologous desensitization due to PGE2 was significantly attenuated [3].
• PTH/PTHrP receptor gene expression was evaluated in situ in avian epiphyseal growth plates taken from normal, rachitic and tibial dyschondroplasia (TD) afflicted chicks induced by thiram or by genetic selection [9].
• However, it also was demonstrated that a surge of PTH is not necessary for recovery from the EGTA-induced hypocalcemia [10].

Biological context of PTH

• The middle and carboxyl-terminal portions of chicken PTH, however, differ considerably from the mammalian hormones and include deletions of sequences conserved in mammalian PTH and insertions of novel peptide sequences [11].
• In order to characterize an avian parathyroid hormone gene, a lambda gt10 cDNA library constructed from chicken parathyroid gland mRNA was screened with a human preproparathyroid hormone (preproPTH) cDNA probe [11].
• In conclusion, these data indicate that PTH stimulation of bsp gene expression is specific to osteoblasts and mediated by changing cellular cAMP/PKA levels [12].
• Co-transfection of an expression plasmid encoding heat-stable inhibitor of cAMP-dependent protein kinase, a peptide inhibitor of PKA, decreased both the basal and PTH-induced bsp transcription, while co-expression of the catalytic subunit of PKA-induced bsp expression 3-fold [12].
• A half-cAMP response element site in the bsp promoter was identified as the cis-acting element that mediated the PTH response by the transient transfections with reporter constructs containing nested deletions of the promoter or a heterologous promoter containing the cAMP response element [12].

Anatomical context of PTH

• Undifferentiated cells obtained from limb buds prior to appearance of hormonal responsiveness were cultured and were found to develop a PTH-activated adenylate cyclase in vitro [13].
• The enzyme did not respond to other hormones, and myoblast cultures did not develop a PTH-activated adenylate cyclase, indicating that a true bone adenylate cyclase was being measured [13].
• Parathyroid hormone (PTH) caused osteoclasts to increase in area about 40%, and calcitonin (CT) caused a decrease in area also of about 40% [14].
• The results suggest that the PTH receptor binding in the calvaria and the kidney is affected by ovarian steroid hormones and may play a role in maintaining the calcium homeostasis in the egg-laying hen [15].
• Using the P19 EC cell line, we have characterized promoter elements of the murine PTH/PTHrP-receptor gene that are involved in this RA-induced expression [16].

Associations of PTH with chemical compounds

• With deprivation of vitamin D, the progressive increase in 1 alpha-hydroxylase correlated inversely with circulating levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D), and the decreasing calcemic response to PTH correlated inversely with the responsiveness of 1 alpha-hydroxylase to PTH (in chicks deprived of vitamin D for 1-10 d) [2].
• In addition, a temporal sequence of development of hormone response was observed, with a PTH-activated adenylate cyclase appearing earlier than the calcitonin-activated enzyme [13].
• PTH and PGE2 treatment did not affect the cAMP response to forskolin and cholera toxin [3].
• Subsequent addition of dibutyryl cyclic AMP to PTH- or to CT-treated cells resulted in a further change of 40 and 30%, respectively [14].
• The cells were treated with acetazolamide (10 x 4 M and 10(-7) M), CT (1 mU/ml and 0.31 mU/ml) and PTH (6.5 U/ml and 0.40 U/ml) for 1, 3, 6, and 18 hr [17].

Physical interactions of PTH

• Inhibition of PTH receptor binding and PTH mediated adenylate cyclase activity by somatostatin [18].

Regulatory relationships of PTH

• CT also stimulated the proteoglycan synthesis only in the diaphysis but the stimulation was less potent (133% of control) than PTH (650% of control) or dibutyryl cyclic AMP (625% of control) [19].

Other interactions of PTH

• They further suggest that although protein kinase C is capable of stimulating the gene by itself, it plays a minimal role in mediating the PTH induction of bone sialoprotein [12].
• Parathyroid hormone (PTH) receptor bindings were examined in the membrane fraction of the calvaria and the kidney of the hen by the use of [125I]PTH-related protein (PTHrP) binding assays [15].
• In another experiment in which no vitamin D source was given and the diets contained increasing levels of dietary calcium, plasma calcium increased significantly (5.5 vs. 7 mg/dl), while PTH mRNA decreased by 40% and VDR mRNA increased by 60% [20].
• PTH also affected matrix production by the growth plate chondrocytes causing a twofold stimulation of proteoglycan synthesis as determined by the rate of 35SO4 incorporated into matrix macromolecules [21].
• In addition, isolated avian flexor digitorum profundus TSC and TIF cells were subjected to cyclic stretching at 1 Hz, 5% average elongation for 6 h, +/- PDGF-BB, IGF-I, TGF-beta 1, PTH, estrogen, PGE2, or no drug and/or no load. mRNA was then collected and samples were subjected to differential display analysis [22].

Analytical, diagnostic and therapeutic context of PTH

• Northern blot analysis of chicken parathyroid mRNA, using both bovine and chicken cDNA probes, showed that the mRNA (2.3 kilobases) for chicken hormone precursor was approximately 3 times the size of mRNA for mammalian prepro-PTH [1].
• The presence of PTH in the cocultures or conditioned media from PTH-treated calvariae did not significantly alter the level of expression [23].
• The time course of OC marker expression was monitored by ELISA and the requirement for live bone and PTH was investigated [23].
• Treatment with PTH caused 30-60% increase in PKI activity, and cell cultures that were grown in medium containing either 0.5 or 2 mM calcium chloride had similar PKI activities [24].
• PTH bioactivity during the egg-laying cycle of the chicken has been measured by the cytochemical bioassay for PTH [25].

References