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Clinical Biochemistry Jun 2007It is now 43 years since Berson and Yalow published the first radio-immunoassay (RIA) for parathyroid hormone (PTH) [S.A. Berson, R.S. Yalow, G.D. Aurbach, J.T. Potts,... (Review)
Review
It is now 43 years since Berson and Yalow published the first radio-immunoassay (RIA) for parathyroid hormone (PTH) [S.A. Berson, R.S. Yalow, G.D. Aurbach, J.T. Potts, Immunoassay of bovine and human parathyroid hormone. Proc Natl Acad Sci U S A 49 (1963) 613-617] [1]. Since then, there have been marked advances in our understanding of this peptide hormone, its mechanism of action and biological regulation [J.T. Potts, Parathyroid hormone: past and present. J. Endocrinol. 187 (2005) 311-325] [2]. PTH has become a routine assay in tertiary care hospitals and is an essential element in the management of chronic kidney disease, parathyroid disorders and the investigation of abnormalities in calcium homeostasis. Despite continuing technological advances in PTH measurement, analyte heterogeneity remains a problem, while improved turnaround time and better precision are constantly escalating clinical demands. This mini-review begins with a brief update of current knowledge on PTH, followed by a summary of a recent Ontario-wide External Quality Assurance (EQA) survey, and concludes with comments on utilization trends, current and future.
Topics: Humans; Immunoassay; Intraoperative Care; Luminescent Measurements; Ontario; Parathyroid Hormone; Parathyroidectomy; Postoperative Care; Quality Control
PubMed: 17493603
DOI: 10.1016/j.clinbiochem.2007.03.019 -
Endocrine Reviews Feb 2005PTH is a major systemic regulator of the concentrations of calcium, phosphate, and active vitamin D metabolites in blood and of cellular activity in bone. Intermittently... (Review)
Review
PTH is a major systemic regulator of the concentrations of calcium, phosphate, and active vitamin D metabolites in blood and of cellular activity in bone. Intermittently administered PTH and amino-terminal PTH peptide fragments or analogs also augment bone mass and currently are being introduced into clinical practice as therapies for osteoporosis. The amino-terminal region of PTH is known to be both necessary and sufficient for full activity at PTH/PTHrP receptors (PTH1Rs), which mediate the classical biological actions of the hormone. It is well known that multiple carboxyl-terminal fragments of PTH are present in blood, where they comprise the major form(s) of circulating hormone, but these fragments have long been regarded as inert by-products of PTH metabolism because they neither bind to nor activate PTH1Rs. New in vitro and in vivo evidence, together with older observations extending over the past 20 yr, now points strongly to the existence of novel large carboxyl-terminal PTH fragments in blood and to receptors for these fragments that appear to mediate unique biological actions in bone. This review traces the development of this field in the context of the evolution of our understanding of the "classical" receptor for amino-terminal PTH and the now convincing evidence for these receptors for carboxyl-terminal PTH. The review summarizes current knowledge of the structure, secretion, and metabolism of PTH and its circulating fragments, details available information concerning the pharmacology and actions of carboxyl-terminal PTH receptors, and frames their likely biological and clinical significance. It seems likely that physiological parathyroid regulation of calcium and bone metabolism may involve receptors for circulating carboxy-terminal PTH ligands as well as the action of amino-terminal determinants within the PTH molecule on the classical PTH1R.
Topics: Amino Acid Sequence; Animals; Binding Sites; Conserved Sequence; Humans; Intestines; Molecular Sequence Data; Osteoclasts; Parathyroid Hormone; Peptide Fragments; Receptors, Parathyroid Hormone
PubMed: 15689574
DOI: 10.1210/er.2003-0024 -
Terapevticheskii Arkhiv 2017Hypoparathyroidism is an endocrine disease that results from deficiency or complete absence of parathyroid hormone (PTH), a biologically active 84-amino acid... (Review)
Review
Hypoparathyroidism is an endocrine disease that results from deficiency or complete absence of parathyroid hormone (PTH), a biologically active 84-amino acid polypeptide. Standard therapy for chronic hypoparathyroidism includes oral calcium salts and active vitamin D metabolites and is aimed at maintaining a balance between optimal near-normal serum calcium concentration and normocalcuria. Traditional treatment regimens not always lead to the compensation for calcium and phosphorus metabolism. Until recently, hypoparathyroidism is the only endocrine disorder that has not been treated with the recombinant hormone. To date, two recombinant PTH forms have been synthesized, which can be used as pathogenetic therapy for hypoparathyroidism. This review is dedicated to replacement therapy for hypoparathyroidism, by using both the full-length PTH molecule (1-84) and its shorter, but fully active, PTH form (1-34). This review considers stages in the developmental of hormone replacement therapy for hypoparathyroidism, discusses the most rational dosing regimens, and compares their efficacy and safety, as well as prospects for the development of this area.
Topics: Hormone Replacement Therapy; Humans; Hypoparathyroidism; Medication Therapy Management; Parathyroid Hormone; Recombinant Proteins
PubMed: 29171476
DOI: 10.17116/terarkh2017891080-86 -
Canadian Journal of Surgery. Journal... Jul 1978Our expanding knowledge of the physiologic and biochemical factors governing calcium homeostasis has improved our capacity to evaluate hypercalcemia, of which an... (Review)
Review
Our expanding knowledge of the physiologic and biochemical factors governing calcium homeostasis has improved our capacity to evaluate hypercalcemia, of which an increased incidence is being discovered through the widespread use of multiphasic screening. Consequently, we are diagnosing mild forms of hyperparathryoidism more often than formerly. The enhanced recognition of virtually symptom-free hyperparathyroidism presents a problem in patient management because the natural history of this form of hyperparathyroidism is unknown and the pathologic lesion underlying the condition may be ambiguous, resulting in difficult decisions in surgical management. Further study is required to resolve this issue in order to provide optimal care for the affected individual.
Topics: Animals; Calcium; Diagnosis, Differential; Homeostasis; Humans; Hypercalcemia; Hyperparathyroidism; Parathyroid Hormone; Vitamin D
PubMed: 354759
DOI: No ID Found -
Recent Progress in Hormone Research 1976
Review
Topics: Amino Acid Sequence; Animals; Carcinoma, Krebs 2; Cattle; Cell-Free System; Chemical Phenomena; Chemistry; Endocrine Glands; Humans; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Peptide Hydrolases; Peptides; Protein Biosynthesis; Proteins; RNA, Messenger; Radioimmunoassay
PubMed: 801192
DOI: 10.1016/b978-0-12-571133-3.50013-1 -
Endocrine Reviews Dec 1993
Review
Topics: Animals; Bone Diseases, Metabolic; Bone and Bones; Humans; Hyperparathyroidism; Parathyroid Hormone; Second Messenger Systems
PubMed: 8119233
DOI: 10.1210/edrv-14-6-690 -
Proceedings of the National Academy of... Dec 1971Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the...
Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood (obtained by venous catheterization) from patients with hyperparathyroidism, as well as from calves and from cattle. Hormone secreted in vivo from normal bovine parathyroid glands and from human parathyroid adenomas is similar in size to the 84-amino-acid peptide (molecular weight of 9500) extracted from the parathyroids. However, much of the immunoreactive parathyroid hormone present in the peripheral circulation of man and cattle is smaller than the extracted or secreted hormone; it elutes from gel columns at a position corresponding to a molecular weight of about 7000. The immunological characteristics of extracted and secreted hormone are identical, while hormone in the general circulation is immunologically dissimilar to extracted and secreted hormone. The results indicate that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.
Topics: Amino Acids; Animals; Cattle; Chromatography, Gel; Guinea Pigs; Humans; Hyperparathyroidism; Immune Sera; Iodine Isotopes; Parathyroid Glands; Parathyroid Hormone; Radioimmunoassay; Species Specificity
PubMed: 5289243
DOI: 10.1073/pnas.68.12.2986 -
Endocrinology Nov 1995
Review
Topics: Animals; Humans; Parathyroid Hormone; Peptide Fragments
PubMed: 7588199
DOI: 10.1210/endo.136.11.7588199 -
Small (Weinheim An Der Bergstrasse,... Feb 2020Osteogenesis, osteoclastogenesis, and angiogenesis are the most important processes in bone repair. Parathyroid hormone (PTH) has pro-osteogenic, pro-osteoclastogenic,...
Osteogenesis, osteoclastogenesis, and angiogenesis are the most important processes in bone repair. Parathyroid hormone (PTH) has pro-osteogenic, pro-osteoclastogenic, and proangiogenic effects and may be a candidate for use in bone defect repair. However, the local application of PTH to bone defects is counterproductive due to its excessive osteoclastic and bone resorptive effects. In this study, a PTH derivative, PTHrP-2, is developed that can be applied to local bone defects. First, a modified peptide with a calcium-binding repeat glutamine tail undergoes controlled local release from a ceramic material and is shown to be a better fit for the repair process than the unmodified peptide. Second, the modified peptide is shown to have strong pro-osteogenic activity due to mineralization and its facilitation of serine (Ser) phosphorylation. Third, the modified peptide is shown to maintain the pro-osteoclastogenic and proangiogenic properties of the unmodified peptide, but its pro-osteoclastogenic activity is reduced compared to that of the unmodified peptide. The reduced pro-osteoclastogenic and increased pro-osteogenic properties of the modified peptide reverse the imbalance between osteoblasts and osteoclasts with local PTH application and shift bone resorption to bone regeneration.
Topics: Bone Density Conservation Agents; Bone Regeneration; Bone Remodeling; Bone Resorption; Humans; Neovascularization, Physiologic; Osteoblasts; Osteoclasts; Parathyroid Hormone
PubMed: 31962381
DOI: 10.1002/smll.201905876 -
Nihon Rinsho. Japanese Journal of... Aug 2005
Review
Topics: Biomarkers; Bone and Bones; Calcium; Diagnosis, Differential; Humans; Hypercalcemia; Hypocalcemia; Immunoradiometric Assay; Neoplasms; Parathyroid Diseases; Parathyroid Hormone; Radioimmunoassay; Renal Dialysis; Thyroid Function Tests
PubMed: 16149511
DOI: No ID Found