Parathyroid hormone /

Detalles Bibliográficos
Clasificación:Libro Electrónico
Otros Autores: Litwack, Gerald
Formato: eBook
Idioma:Inglés
Publicado: Cambridge, MA : Academic Press, 2022.
Colección:Vitamins and hormones ; v. 120.
Temas:
Parathyroid hormone.
Parathyroid Hormone
Parathormone.
Parathyroid hormone
Acceso en línea:Texto completo
Tabla de Contenidos:
  • 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.
  • 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.

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