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Parathyroid hormone sensitizes long bones to the stimulation of bone resorption by 1,25‐dihydroxyvitamin D 3
Author(s) -
van Leeuwen J. P. T. M.,
Birkenhäger J. C.,
Bos M. P.,
van der Bemd G. J. C. M.,
HerrmannErlee M. P. M.,
Pols H. A. P.
Publication year - 1992
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650070309
Subject(s) - bone resorption , parathyroid hormone , endocrinology , resorption , medicine , osteoclast , prostaglandin e2 , chemistry , stimulation , calcitriol , prostaglandin e , calcium , vitamin d and neurology , receptor
Abstract In response to hypocalcemia the serum PTH level increases rapidly followed by a PTH‐induced rise in 1,25‐dihydroxyvitamin D 3 [1,25‐(OH) 2 D 3 ] production. Therefore, bone is first exposed to increased PTH levels before increased 1,25‐(OH) 2 D 3 levels. In the present study the effect of pretreatment with PTH on 1,25‐(OH) 2 D 3 ‐induced bone resorption was examined. Bone resorption was measured as release of prelabeled 45 Ca during culture from 17‐day‐old fetal mice radii/ulnae and metatarsals. Radii/ulnae and metatarsals are characterized by differences in development. In radii/ulnae mature osteoclasts are present, whereas in metatarsals only different stages of preosteoclasts can be found. Preincubation for 24 h but not 4 h with PTH increases the stimulation of bone resorption by 1,25‐(OH) 2 D 3 in fetal radii/ulnae but not in metatarsals. Coincubation of PTH and 1,25‐(OH) 2 D 3 did not result in a significant change in bone resorption compared to 1,25‐(OH) 2 D 3 alone. The observed difference in the effect of pretreatment with PTH between radii/ulnae and metatarsals indicates that PTH does not stimulate the development of early osteoclast precursors but that a certain level of differentiation of the osteoclast precursor is required. Pretreatment with prostaglandin E 2 resulted in an effect similar to that of PTH. Inhibition of prostaglandin synthesis by indomethacin prevented the potentiation of 1,25‐(OH) 2 D 3 ‐induced bone resorption by pretreatment with PTH. Thus, the present study demonstrates that PTH sensitizes responses to 1,25‐(OH) 2 D 3 . PTH must be present before 1,25‐(OH) 2 D 3 to observe a potentiation of 1,25‐(OH) 2 D 3 ‐induced bone resorption. Local production of prostaglandins seems to be involved in this action of PTH. Taken together, these data suggest that besides increased renal production of 1,25‐(OH) 2 D 3 PTH also sensitizes bone for the 1,25‐(OH) 2 D 3 ‐induced bone resorption.

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