{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:39:04Z","timestamp":1790876344516,"version":"4.1.0"},"reference-count":213,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parathyroid hormone (PTH) and the paracrine factor, PTH-related protein (PTHrP), have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein-coupled receptor, PTH1R, that predominantly uses the cyclic adenosine monophosphate-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two. Mouse genetic studies show that PTHrP is essential for endochondral bone lengthening in the fetus and is essential for bone remodeling. In contrast, the main postnatal function of PTH is hormonal control of calcium homeostasis, with no evidence that PTHrP contributes. Pharmacologically, amino-terminal PTH and PTHrP peptides (teriparatide and abaloparatide) promote bone formation when administered by intermittent (daily) injection. This anabolic effect is remodeling-based with a lesser contribution from modeling. The apparent lesser potency of PTHrP than PTH peptides as skeletal anabolic agents could be explained by lesser bioavailability to PTH1R. By contrast, prolongation of PTH1R stimulation by excessive dosing or infusion, converts the response to a predominantly resorptive one by stimulating osteoclast formation. Physiologically, locally generated PTHrP is better equipped than the circulating hormone to regulate bone remodeling, which occurs asynchronously at widely distributed sites throughout the skeleton where it is needed to replace old or damaged bone. While it remains possible that PTH, circulating within a narrow concentration range, could contribute in some way to remodeling and modeling, its main physiological role is in regulating calcium homeostasis.<\/jats:p>","DOI":"10.1210\/endrev\/bnab005","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T05:01:40Z","timestamp":1612933300000},"page":"383-406","source":"Crossref","is-referenced-by-count":112,"title":["Physiological and Pharmacological Roles of PTH and PTHrP in Bone Using Their Shared Receptor, PTH1R"],"prefix":"10.1210","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-1291","authenticated-orcid":false,"given":"T John","family":"Martin","sequence":"first","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria, Australia"},{"name":"The University of Melbourne, Department of Medicine at St. Vincent\u2019s Hospital, Fitzroy, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1421-8468","authenticated-orcid":false,"given":"Natalie A","family":"Sims","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria, Australia"},{"name":"The University of Melbourne, Department of Medicine at St. Vincent\u2019s Hospital, Fitzroy, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9692-048X","authenticated-orcid":false,"given":"Ego","family":"Seeman","sequence":"additional","affiliation":[{"name":"The University of Melbourne, Department of Medicine at Austin Health, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"issue":"3","key":"2021120109105932600_CIT0001","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1677\/joe.1.06057","article-title":"Parathyroid hormone: past and present","volume":"187","author":"Potts","year":"2005","journal-title":"J Endocrinol."},{"issue":"4817","key":"2021120109105932600_CIT0002","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1126\/science.3616618","article-title":"A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression","volume":"237","author":"Suva","year":"1987","journal-title":"Science."},{"issue":"1","key":"2021120109105932600_CIT0003","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1152\/physrev.1996.76.1.127","article-title":"Defining the roles of parathyroid hormone-related protein in normal physiology","volume":"76","author":"Philbrick","year":"1996","journal-title":"Physiol Rev."},{"issue":"Suppl","key":"2021120109105932600_CIT0004","first-page":"S23","article-title":"Parathyroid hormone-related protein: hormone and cytokine","volume":"154","author":"Martin","year":"1997","journal-title":"J Endocrinol."},{"issue":"19","key":"2021120109105932600_CIT0005","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis","volume":"344","author":"Neer","year":"2001","journal-title":"N Engl J Med."},{"key":"2021120109105932600_CIT0006","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0002-9343(61)90068-7","article-title":"Parathyroid hormone. 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