What question did this study set out to answer?

To identify the intracellular pathways and molecular mechanisms responsible for homologous down-regulation of parathyroid hormone (PTH)/PTH-related peptide receptor mRNA in human osteoblastic cells.

April 1, 1994Endocrinology

Role of protein kinase-A in homologous down-regulation of parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acid in human osteoblast-like SaOS-2 cells.

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To identify the intracellular pathways and molecular mechanisms responsible for homologous down-regulation of parathyroid hormone (PTH)/PTH-related peptide receptor mRNA in human osteoblastic cells.
Cultured wild-type human osteoblastic SaOS-2 cells and a mutant cAMP-resistant subclone (Ca4A) under stimulation with human PTH-(1-34), DBcAMP, forskolin, phorbol esters, or calcium mobilizers.
Assessed steady-state levels of the 2.2- to 2.5-kilobase PTH/PTHrP receptor mRNA transcript across 4 to 24 hours using Northern blot analysis.
Co-treated cells with transcriptional inhibitor actinomycin-D or translational inhibitor cycloheximide to evaluate requirements for de novo RNA and protein synthesis.
Treatment with hPTH-(1-34) (10^-7 M) significantly reduced PTH/PTHrP receptor mRNA by approximately 50% at 24 hours in wild-type cells, which was mimicked by DBcAMP and forskolin.
Down-regulation by hPTH-(1-34), DBcAMP, or forskolin was almost completely abolished in cAMP-resistant Ca4A cells, and actinomycin-D blocked the decrease while cycloheximide did not.
Intracellular calcium mobilizers and C-terminal PTH fragments failed to alter receptor mRNA expression, whereas active phorbol esters induced rapid down-regulation within 4–6 hours.

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Implication

In vitro study demonstrates that cAMP-dependent protein kinase mediates PTH receptor down-regulation in osteoblasts, indicating a delayed transcriptional response.

Cite This Study

Fukayama et al. (1994) studied this question.

synapsesocial.com/papers/6a904df5ccd91641af4dd187 https://doi.org/10.1210/endo.134.4.8137752

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Implication

In vitro study demonstrates that cAMP-dependent protein kinase mediates PTH receptor down-regulation in osteoblasts, indicating a delayed transcriptional response.

Role of protein kinase-A in homologous down-regulation of parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acid in human osteoblast-like SaOS-2 cells.

Key Points

Discussion

Implication

Cite This Study

Role of protein kinase-A in homologous down-regulation of parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acid in human osteoblast-like SaOS-2 cells.

Key Points

Discussion

Implication

Cite This Study

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