Parathyroid Hormone

Name: Parathyroid Hormone
Brand: Academic Press
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Erschienen am 9. August 2022

390 Seiten

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Inhalt

Intro
Parathyroid Hormone
Copyright
Contents
Contributors
Preface
Chapter One: Structural pharmacology of PTH and PTHrP
1. Evolutionary biology of PTH and PTHrP
2. PTH mutations
3. PTHrP mutations
4. PTH and PTHrP pharmacology
4.1. PTH and PTHrP action is not identical
4.2. PTH and PTHrP signaling
4.3. PTH and PTHrP peptides providing insight into physiology
Acknowledgments
References
Chapter Two: Salt inducible kinases and PTH1R action
1. Parathyroid hormone and PTH1R biology
2. PTH as anabolic therapies for osteoporosis
3. PTH action in osteocytes
4. Salt inducible kinases
5. Role of salt inducible kinases in responses to PTH in bone
6. Role of salt inducible kinases in responses to PTH in cartilage
7. Do salt inducible kinases participate in the renal actions of PTH?
8. PTH stimulates Cyp27b1 expression
9. PTH decreases phosphate reabsorption in proximal tubule
10. PTH increases calcium reabsorption in distal tubule
11. Summary and future directions
References
Chapter Three: Physiological regulation of phosphate homeostasis
1. Introduction
2. An overview of phosphate homeostasis
3. Intestinal phosphate absorption
4. Transcellular intestinal phosphate absorption and the role of NaPi-IIb
4.1. Other sodium-dependent transporters involved in transcellular phosphate absorption
4.2. Endocrine control of transcellular phosphate absorption
4.3. Paracellular intestinal phosphate absorption
4.4. Characterization and regulation of the paracellular pathway
5. Renal phosphate reabsorption
5.1. Regulation of renal phosphate reabsorption
6. Phosphate imbalance
6.1. Targeting renal phosphate transport
6.2. Targeting intestinal phosphate transport
Conflict of interest
References
Chapter Four: The parathyroid glands and parathyroid hormone: Insights from PTH gene mutations
1. History of the parathyroid gland and parathyroid hormone
2. Sequence and structure of the PTH gene
3. Synthesis, processing, and secretion of PTH
4. Chromosomal rearrangement of the PTH gene
4.1. PTH promotor/cyclin D1 rearrangement
4.2. DNA rearrangement in the upstream regulatory region of the PTH gene
5. Intragenic polymorphisms of the PTH gene
6. Mutations in the PTH signal peptide
6.1. Heterozygous PTH C18R mutation
6.2. Homozygous PTH S23P mutation
6.3. Homozygous PTH S23X mutation
6.4. Heterozygous p.Met1_Asp6del PTH mutation
6.5. Heterozygous M14K PTH mutation
7. PTH exon skipping mutation
7.1. Homozygous PTH exon 2 skipping mutation
8. Mutations in the mature PTH peptide
8.1. Heterozygous PTH R83X mutation (R52X in mature PTH)
8.2. Homozygous PTH R56C mutation (R25C in mature PTH)
8.3. Homozygous PTH S32P mutation (S1P in mature PTH)
9. Conclusions and future directions
Acknowledgments
Conflicts of interest
References
Chapter Five: Modulation of PTH1R signaling by an extracellular binding antibody
1. Introduction
1.1. Parathyroid hormone, parathyroid 1 receptor and bone development
1.2. The PTH1R
1.3. PTH1R and biased agonism
1.4. Monoclonal antibodies
2. Results
2.1. Antibody discovery overview
2.2. ECD-ScFvhFc and PTH1R signaling
2.3. Characterization of antibody binding to full length receptor
2.4. Mapping the ECD-scFvhFc binding site
3. Discussion
Acknowledgments
References
Chapter Six: Parathyroid hormone-related protein (PTHrP) and malignancy
1. Background
1.1. Calcium metabolism and regulation
1.1.1. Bone metabolism
1.1.2. Renal regulation
1.2. Discovery of PTHrP
1.3. Cloning of PTHrP
1.4. Structure of PTHrP
1.4.1. Gene structure
1.4.2. Functional domains of PTHrP
1.4.2.1. Interactions with cell surface receptors (via amino-terminal domain)
1.4.2.2. Other functional domains of PTHrP
1.4.2.3. Mid-molecule portion (residues 35-84)
1.4.2.4. Nuclear localization sequence (residues 87-107)
1.4.2.5. COOH-terminal fragments (residues 107 and beyond)
1.4.2.6. Detection of PTHrP
2. Characterization of MAH
2.1. Differences between PTHrP and PTH manifestations
2.2. Pathophysiologies of MAH (PTHrP associated and unassociated)
2.2.1. Humoral hypercalcemia of malignancy (HHM)
2.2.2. Osteolytic metastases with local release of cytokines
2.2.3. Tumor production of 1,25D
2.2.4. Tumor production and ectopic secretion of PTH
3. Role of PTHrP in tumor progression
3.1. Expression and regulation of PTHrP in tumors
3.2. Relationship of PTHrP with the bone microenvironment
3.3. Extra-skeletal actions of PTHrP in malignancy
4. Clinical implications of MAH
4.1. Clinical manifestations of hypercalcemia
4.2. Diagnostic approach and investigation of hypercalcemia
4.3. Therapeutic modalities for MAH and skeletal metastases
4.3.1. Clinically approved therapies and their limitations
4.3.2. Investigational approaches to controlling PTHrP production and action
4.3.3. Potential non-skeletal roles for anti-PTHrP therapies
5. Conclusion
Acknowledgments
Disclaimer
References
Further reading
Chapter Seven: Parathyroid hormone-related protein (PTHrP)-dependent modulation of gene expression signatures in cancer cells
1. Parathyroid hormone-related protein (PTHrP): A brief insight into its structure and function
2. Bone cancer cells
2.1. Osteosarcoma cells
2.2. Giant bone tumor cells
3. Breast cancer cells
3.1. 8701-BC cell line
3.2. MDA-MB231 cell line
3.3. MCF-7 cell line
3.4. Animal studies
4. Cancer cells of the digestive system
4.1. Colorectal cancer cells
4.2. Liver cancer cells
4.3. Oral cancer cells
5. Leukema/lymphoma adult T-cells
6. Prostate cancer cells
7. Conclusions
References
Chapter Eight: Parathyroid hormone-related protein in breast cancer bone metastasis
1. Introduction
2. Discovery and nature of PTHrP
3. Breast cancer and bone metastases before PTHrP
4. Breast biology, breast cancer and PTHrP
5. Regulation of PTHrP in tumor-induced bone disease
5.1. TGF-ß and the vicious cycle: Fig. 1 about here
5.2. Transcriptional regulation of PTHrP expression by Gli2
6. Crosstalk with the microenvironment regulation of PTHrP
Funding information
References
Chapter Nine: Stimulation of osteoclast formation and bone resorption by glucocorticoids: Synergistic interactions with t ...
1. Introduction
2. Pathogenetic mechanisms causing increased bone resorption in glucocorticoid-induced osteoporosis
2.1. Studies in humans
2.2. Studies in mice
2.3. Effects by GCs in bone organ cultures
2.4. Direct effects of GCs on osteoclasts and osteoclast progenitors
2.5. Indirect effects by GCs on osteoclast formation through RANKL and OPG
3. Glucocorticoid receptor
4. Interaction between glucocorticoids and calcium regulating hormones
5. Concluding remarks/summary
References
Chapter Ten: Evolution of intra-operative parathyroid hormone and its application in parathyroid surgery
1. Discovery of the parathyroid gland
2. History of parathyroid hormone
3. Early parathyroid surgery
4. Evolution of intraoperative parathyroid hormone
5. Dissemination of intraoperative parathyroid hormone
6. Use of parathyroid hormone testing in reoperative cases
6.1. Radio-guided selective venous sampling
6.2. Bilateral internal jugular venous sampling
6.3. USG guided parathyroid biopsy with PTH washout
7. Elevated parathyroid hormone levels postsurgery
8. Future directions
References
Chapter Eleven: Gene expression profiles in parathyroid adenoma and normal parathyroid tissue
1. Introduction
1.1. Synthesis of PTH
1.2. Regulation of PTH secretion
2. Summary of germline and somatic genetics in sporadic parathyroid adenoma
3. Comparative genomic expression
3.1. Genes involved in cell cycle regulation
3.2. Genes involved in growth factors
3.3. Genes involved in apoptotic pathway
3.4. Genes involved in PTH synthesis or regulation pathway
3.4.1. GCM2
3.4.2. CaSR
3.4.3. Klotho
3.5. Next-generation sequencing analysis
3.6. Differential microRNA expression
Acknowledgment
References
Chapter Twelve: Renal hyperparathyroidism
1. Pathophysiology of renal hyperparathyroidism
1.1. Histology of parathyroid gland (Fig. 1)
1.2. Klotho-FGF-23-endocrine axes and calcium-phosphate homeostasis in renal hyperparathyroidism (Fig. 2) (Brown et al., ...
2. Causes of renal hyperparathyroidism
2.1. Hypocalcemia
2.2. Decreased circulating calcitriol levels
2.3. Hyperphosphatemia
2.4. Parathyroid cell proliferation and tumorigenesis
3. Medical treatment of renal hyperparathyroidism (Table 1)
3.1. Management goals
3.2. Diet therapy and phosphorus restriction
3.3. Phosphorus adsorbents
3.4. Vitamin D receptor activators
3.5. Drugs for osteoporosis
3.6. Calcimimetics
3.7. Parathyroidectomy
3.7.1. Surgical procedure
3.7.2. An algorithm to identify parathyroid glands
3.7.3. Intraoperative intact PTH monitoring
3.7.3.1. The necessity of intraoperative PTH monitoring
3.7.4. Measurement of intact PTH
3.7.5. Intraoperative intact PTH monitoring for renal hyperparathyroidism
3.8. Parathyroid carcinoma
4. Renal bone disease
4.1. Impact of treatments on hyperparathyroid bone disease
4.1.1. Parathyroidectomy
4.2. Bone disease caused by long-term hypoparathyroidism
4.3. Osteocytic perilacunar/canalicular turnover
Acknowledgments
References
Further reading
Chapter Thirteen: Primary cilia and PTH1R interplay in the regulation of osteogenic actions
1. Introduction to primary cilia structure, biogenesis, intra-ciliary transport and molecular mechanotransducers in bone
2. Role of primary cilia in bone
3. Primary cilia-depending signaling pathways associated with activation of PTH1R in osteogenesis: Hedgehog and TGF-ß/BMP ...
3.1. PTH1R signaling pathway
3.2. Hedgehog signaling
3.3. TGF-ß/BMP signaling
4. Primary cilia and PTH1R interactions in osteogenesis
4.1. Osteogenic actions during development: Endochondral ossification and postnatal growth plate
4.2. Osteogenic actions in adult bone cells
5. Conclusions
Acknowledgments
References

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