Disease relevance of PTHLH

• METHODS: Expanded BMSCs derived from patients with hip OA were seeded onto polyglycolic acid scaffolds and differentiated using transforming growth factor beta3 in the presence or absence of parathyroid hormone-related protein (PTHrP) to regulate hypertrophy [1].

High impact information on PTHLH

• 1,25(OH)2D3 also decreased secretion of PTHrP by BVSMCs in a dose-dependent manner and depressed its gene expression [2].
• The addition of PTHrP to aza-C-treated cultures at day 14 led to the down-regulation of type X collagen by 6-fold, showing type X collagen expression is under the control of PTHrP as in vivo [3].
• PTHrP (1-34) and PTH (1-34) dose-dependently inhibited BVSMC calcification [4].
• We demonstrated that the expression of PTHrP decreased in the progression of bovine vascular smooth muscle cell (BVSMC) calcification and that inhibition of calcification by etidronate (EHDP) and levamisole restored PTHrP secretion, suggesting that the expression of PTHrP is associated with calcification [4].
• We measured the PTH-rP content of milk from 42 Jersey cows from a single farm in various stages of lactation [5].

Biological context of PTHLH

• Expression of PTHrP mRNA was demonstrated in the mammary gland during late pregnancy and throughout lactation in cows [6].
• A 1065 bp clone (bP1) for bovine PTHrP was isolated from a brain cDNA library [6].
• The 5'- and 3'-UTRs of bovine brain PTHrP have a high degree of homology to exons 4 and 9 of human PTHrP respectively [6].
• The predicted amino acid sequence of bovine PTHrP was 72-92% homologous to the sequences of chicken, rat, mouse, human, and canine PTHrP with the highest sequence divergence present in the C-terminal region of the peptide [6].
• During periparturient period, relative PTHrP mRNA level was remarkably low before the parturition in a Jersey and a Holstein cow, however, both levels were gradually increased and reached a peak level at 5-6 weeks after the parturition [7].

Anatomical context of PTHLH

• Expression of PTHrP mRNA was localized to secretory and ductular epithelial cells within the lactating mammary gland, as detected using in situ hybridization [6].
• Colostrum (first milk) contained 56 +/- 12 ng/ml immunoreactive PTH-rP (iPTH-rP) [5].
• Addition of 10% fetal calf serum to serum-deprived endothelial cells did not significantly increase PTHrP-like immunoreactivity [8].
• Supplementation of serum-free cSOFMaa oocyte maturation medium with PTHrP (1-141) resulted in a concentration-dependent increase in development to the blastocyst stage in vitro [9].
• The results suggest that granulosa cells may be a primary site of PTHrP production and release [9].

Associations of PTHLH with chemical compounds

• Interestingly, PTHrP production by BVSMC dramatically increased in the presence of EHDP, and PTHrP (7-34) partially antagonized the inhibitory effect of EHDP on BVSMC calcification [4].
• In proximal convoluted tubules PTH and PTHrP stimulated adenylate cyclase to the same extent and with similar potencies [10].
• Similarly, PTH-rP secretion was not influenced by other known PTH secretagogues such as c-AMP or isoproterenol [11].

Regulatory relationships of PTHLH

• Prolactin stimulated PTHrP production approximately 50% on Days 6-14 [12].
• We conclude that PTH-rP is not secreted from parathyroid cells via the regulated pathway utilizing PTH secretory granules [11].

Other interactions of PTHLH

• PTHrP production was increased approximately 100% by treatment with epidermal growth factor (10 ng/ml) for 2 d [12].

Analytical, diagnostic and therapeutic context of PTHLH

• RT-PCR using region-specific oligonucleotide primers derived from bP1 demonstrated that PTHrP mRNA transcripts in bovine brain and lactating mammary gland utilize the same 5'- and 3'-UTRs [6].
• Immunohistochemistry demonstrated positive staining for PTHrP and cytokeratin in both mammary epithelial and myoepithelial cells and alpha-smooth muscle actin in myoepithelial cells [12].
• Plasma concentration of PTHrP was detected in 11 of 21 cows by use of an immunoradiometric assay (range, 0.45 to 1.82 pmol/L) [13].
• PTHrP production was measured by N-terminal radioimmunoassay and bioassay (increased cAMP levels in ROS 17/2.8 osteoblast-like cells) [12].

References