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Endocrine Practice : Official Journal... 2011To review the history and application of laboratory assays for the measurement of parathyroid hormone. (Review)
Review
OBJECTIVE
To review the history and application of laboratory assays for the measurement of parathyroid hormone.
METHODS
Perinent literature documenting the development of the parathyroid hormone assay was reviewed.
RESULTS
Following its introduction in 1963, the parathyroid hormone assay has evolved into a highly sensitive and specific test. It is now a rapid (less than 20 minutes), relatively inexpensive modality that can be performed without the use of radioactive isotopes. However, the assays commonly used today in clinical practice are still susceptible to certain types of interference and artifact.
CONCLUSIONS
In-house measurement of parathyroid hormone, as well as intraoperative parathyroid hormone monitoring, is now widely available to clinicians in most larger hospitals. This accessibility has greatly facilitated the study and understanding of primary hyperparathyroidism. Despite assay improvements, the measurement of parathyroid hormone in patients with renal disease remains problematic.
Topics: Humans; Models, Biological; Parathyroid Hormone; Radioimmunoassay
PubMed: 21134872
DOI: 10.4158/EP10297.RA -
The Journal of Endocrinology Dec 2005Research on parathyroid hormone (PTH) has undergone four rather distinctive phases, beginning just before the turn of the 20th century. Early debates about the function... (Review)
Review
Research on parathyroid hormone (PTH) has undergone four rather distinctive phases, beginning just before the turn of the 20th century. Early debates about the function of the parathyroids were resolved by 1925, when understanding the role of PTH led to comprehending the action of the glands in calcium physiology. Elucidation of the pathophysiology of hormone excess (severe bone loss) and deficiency (hypocalcemia) continued over the following decades. With the advent of advances in chemical and molecular biology, the structure of PTH and its principal receptor (PTHrP-receptor [PTHR1]) were established. Tests with purified hormonal peptide in humans led to the surprising, even paradoxical, finding that PTH can be used pharmacologically to build bone, providing a dramatic therapeutic impact on osteoporosis. These developments have stimulated the field of calcium and bone biology and posed new questions about the role of PTH as well as possible new directions in therapy.
Topics: Amino Acid Sequence; Anabolic Agents; Humans; Hyperparathyroidism; Hypoparathyroidism; Ligands; Models, Biological; Osteoporosis; Parathyroid Glands; Parathyroid Hormone; Receptors, Parathyroid Hormone; Structure-Activity Relationship
PubMed: 16423810
DOI: 10.1677/joe.1.06057 -
BMJ (Clinical Research Ed.) Jan 1990
Review
Topics: Circadian Rhythm; Humans; Hypercalcemia; Hyperparathyroidism; Male; Parathyroid Hormone
PubMed: 2106926
DOI: 10.1136/bmj.300.6719.210 -
Physiological Reviews Jul 2016Although parathyroid hormone-related protein (PTHrP) was discovered as a cancer-derived hormone, it has been revealed as an important paracrine/autocrine regulator in... (Review)
Review
Although parathyroid hormone-related protein (PTHrP) was discovered as a cancer-derived hormone, it has been revealed as an important paracrine/autocrine regulator in many tissues, where its effects are context dependent. Thus its location and action in the vasculature explained decades-long observations that injection of PTH into animals rapidly lowered blood pressure by producing vasodilatation. Its roles have been specified in development and maturity in cartilage and bone as a crucial regulator of endochondral bone formation and bone remodeling, respectively. Although it shares actions with parathyroid hormone (PTH) through the use of their common receptor, PTHR1, PTHrP has other actions mediated by regions within the molecule beyond the amino-terminal sequence that resembles PTH, including the ability to promote placental transfer of calcium from mother to fetus. A striking feature of the physiology of PTHrP is that it possesses structural features that equip it to be transported in and out of the nucleus, and makes use of a specific nuclear import mechanism to do so. Evidence from mouse genetic experiments shows that PTHrP generated locally in bone is essential for normal bone remodeling. Whereas the main physiological function of PTH is the hormonal regulation of calcium metabolism, locally generated PTHrP is the important physiological mediator of bone remodeling postnatally. Thus the use of intermittent injection of PTH as an anabolic therapy for bone appears to be a pharmacological application of the physiological function of PTHrP. There is much current interest in the possibility of developing PTHrP analogs that might enhance the therapeutic anabolic effects.
Topics: Animals; Bone Development; Bone Diseases; Cartilage; Humans; Mice; Parathyroid Hormone; Parathyroid Hormone-Related Protein
PubMed: 27142453
DOI: 10.1152/physrev.00031.2015 -
Journal of Bone and Mineral Research :... Oct 2002
Review
Topics: Apoptosis; Bone Density; Bone Remodeling; Female; Humans; Hyperparathyroidism; Male; Osteitis Fibrosa Cystica; Osteoblasts; Osteoporosis; Parathyroid Hormone; Periosteum; Receptors, Parathyroid Hormone
PubMed: 12369776
DOI: 10.1359/jbmr.2002.17.10.1741 -
BioDrugs : Clinical Immunotherapeutics,... 2001Parathyroid hormone (PTH), especially intact human PTH [hPTH(1-84)] and its various fragments [hPTH(1-31), (1-34), (1-36), (1-38) and their modifications], has been used... (Review)
Review
Parathyroid hormone (PTH), especially intact human PTH [hPTH(1-84)] and its various fragments [hPTH(1-31), (1-34), (1-36), (1-38) and their modifications], has been used for the treatment of osteoporosis over the last 10 years. Although chronic continuous excess of PTH markedly increases bone resorption, as seen in the typical example of primary hyperparathyroidism and osteitis fibrosa generalisata, intermittent PTH administration has been found to stimulate bone formation in animals, providing a basis for the use of PTH as a therapeutic agent for osteoporosis. In addition to dramatically increasing trabecular bone density and also sustaining cortical bone density, PTH administration increases bone strength and reduces the fracture rate, despite occasional increases in cortical porosity. Administration of PTH in combination with antiresorptive agents such as estrogen, calcitonin, vitamin D and bisphosphonates augments its effect. Because of its bone anabolic action, PTH is expected to be effective for osteoporosis in those of advanced age with suppressed bone remodelling, which might not respond favourably to antiresorptive agents.
Topics: Animals; Humans; Osteoporosis; Parathyroid Hormone
PubMed: 11707147
DOI: 10.2165/00063030-200115110-00003 -
Osteoporosis International : a Journal... Oct 2023Recent studies have demonstrated the positive effects of parathyroid hormone (PTH) on bone healing, and findings support the use of PTH to accelerate bone healing... (Review)
Review
PURPOSE
Recent studies have demonstrated the positive effects of parathyroid hormone (PTH) on bone healing, and findings support the use of PTH to accelerate bone healing following distraction osteogenesis. The goal of this review was to compile and discuss the mechanisms potentially underlying the effects of PTH on newly formed bone following a bone-lengthening procedure incorporating all relevant evidence in both animal and clinical studies.
METHODS
This review summarized all evidence from in vivo to clinical studies regarding the effects of PTH administration on a bone-lengthening model. In addition, a comprehensive evaluation of what is currently known regarding the potential mechanisms underlying the potential benefits of PTH in bone lengthening was presented. Some controversial findings regarding the optimal dosage and timing of administration of PTH in this model were also discussed.
RESULTS
The findings demonstrated that the potential mechanisms associated with the action of PTH on the acceleration of bone regeneration after distraction osteogenesis are involvement in mesenchymal cell proliferation and differentiation, endochondral bone formation, membranous bone formation, and callus remodeling.
CONCLUSIONS
In the last 20 years, a number of animal and clinical studies have indicated that there is a prospective role for PTH treatment in human bone lengthening as an anabolic agent that accelerates the mineralization and strength of the regenerated bone. Therefore, PTH treatment can be viewed as a potential treatment to increase the amount of new calcified bone and the mechanical strength of the bone in order to shorten the consolidation stage after bone lengthening.
Topics: Animals; Humans; Parathyroid Hormone; Bone Regeneration; Bony Callus; Osteogenesis; Osteogenesis, Distraction
PubMed: 37286663
DOI: 10.1007/s00198-023-06809-4 -
Pathobiology Annual 1981Peptide synthesis and the application of a wide range of biological assays have permitted intensive and detailed study of structure-activity relations for parathyroid... (Review)
Review
Peptide synthesis and the application of a wide range of biological assays have permitted intensive and detailed study of structure-activity relations for parathyroid hormone. Within the structure of the hormone molecule reside largely distinct domains critical for receptor binding or activation of adenylate cyclase in addition to receptor binding. Subtle modifications of hormonal structure can cause striking changes in hormone potency or in the nature of the biological properties displayed by such analogs. For parathyroid hormone, structure-activity studies have identified several discrete regions of the molecule that are responsible for independent biological functions. It was determined that these separate functions are displayed in an almost linear fashion along the primary sequence of the hormone--a conceptual framework that has greatly facilitated synthesis of parathyroid hormone analogs. The amino-terminal region of the initially biosynthesized precursor form of parathyroid hormone, pre-proparathyroid hormone, - 31 through - 7, contains a leader or signal sequence. Despite differences in sequence of the parathyroid hormone signal region and other precursor-specific sequences, this region of the molecule possesses biological properties related to intracellular transport and metabolism that appear to be universal for precursor forms of many, if not all, peptide hormones and other secreted proteins. In contrast, the amino-terminal portion of the secreted form of the molecule, sequence region 1-34, has an amino acid sequence that is homologous to that of several peptide hormones, including ACTH, alpha-MSH, beta-MSH, and beta-lipotropin. Yet the biological "message" conveyed by this peptide sequence appears unique to parathyroid hormone. Directions have now been established for the design of hormone inhibitors and for analogs of enhanced biological activity and perhaps even analogs possessing an altered spectrum of biological properties. The rapid advances that are occurring in techniques for peptide synthesis, purification, and analysis; in the variety, sensitivity, and specificity of the increasing number of bioassays; and in the elucidation of peptide and protein conformation may provide further important new directions for analog design. Extension of these investigations of structure and function over the next several years should yield a more sophisticated understanding of the mode of hormone action. In such studies lies the promise of generating highly refined and perhaps clinically useful analogs of parathyroid hormone.
Topics: Adenylyl Cyclases; Amino Acid Sequence; Animals; Cattle; Chemical Phenomena; Chemistry; Enzyme Activation; Humans; Parathyroid Hormone; Peptides; Protein Conformation; Receptors, Cell Surface; Receptors, Parathyroid Hormone; Species Specificity; Structure-Activity Relationship; Swine
PubMed: 6276847
DOI: No ID Found -
Expert Opinion on Biological Therapy Jan 2015Daily subcutaneous injections of parathyroid hormone (PTH), and its synthetic peptide fragment, teriparatide (PTH 1-34, TPTD), have a net anabolic effect on bone and... (Review)
Review
INTRODUCTION
Daily subcutaneous injections of parathyroid hormone (PTH), and its synthetic peptide fragment, teriparatide (PTH 1-34, TPTD), have a net anabolic effect on bone and prevent osteoporotic fractures. TPTD is currently approved for this indication worldwide. Because of the anabolic effect, there is an interest in a role for TPTD (and, where available, human PTH 1-84) in improving bone healing after a fracture. PTH has been studied in animal fracture healing models and in a limited number of human trials. We have reviewed current literature regarding possible mechanisms and efficacy for PTH and TPTD to improve the healing process in the setting of various types of fractures.
AREAS COVERED
Our review focuses first on the role of PTH in normal bone. We then discuss mechanisms of normal bone healing as well as delayed and impaired fracture healing. We summarize pertinent animal data and then review human studies utilizing PTH or TPTD for fracture healing. In particular, we examine unique situations including osteoporotic fractures, diabetes, stress fractures, delayed or poor healing and combination with bisphosphonate therapy.
EXPERT OPINION
Available data indicate there is likely an important role for TPTD and PTH in promoting fracture healing in selected patients, but more clinical trial data are needed.
Topics: Animals; Bone and Bones; Diphosphonates; Fracture Healing; Fractures, Bone; Humans; Parathyroid Hormone; Peptide Fragments; Teriparatide
PubMed: 25363308
DOI: 10.1517/14712598.2015.977249 -
Clinical and Investigative Medicine.... Feb 1993Calcium homeostasis is essential for survival and is primarily achieved through the actions of parathyroid hormone. Parathyroid hormone secretion and synthesis are... (Review)
Review
Calcium homeostasis is essential for survival and is primarily achieved through the actions of parathyroid hormone. Parathyroid hormone secretion and synthesis are primarily regulated by serum calcium levels, although other factors such as vitamin D and neurotransmitters play a role. This review is intended to provide the reader with up to date information on the current state of basic cell regulation research into parathyroid function. While some mention of disease states is made, the focus of this review is on the calcium regulation of parathyroid hormone secretion at the molecular level. Individual sections will discuss calcium-sensing, signal transduction by calcium and other secretagogues, regulation of parathyroid hormone synthesis, and strategies of regulation of parathyroid hormone secretion by calcium. Particular emphasis is given to the calcium-stimulated degradation of parathyroid hormone within the parathyroid as one of the major pathways by which circulating levels of bioactive hormone are controlled.
Topics: Amino Acid Sequence; Animals; Homeostasis; Humans; Molecular Sequence Data; Parathyroid Hormone
PubMed: 8467581
DOI: No ID Found