Serum blocks the osteolytic effect of cortisol in neonatal mouse calvaria.
Chronic glucocorticoid excess is associated with the development of osteoporosis and, in human subjects, there is histomorphometric evidence of increased bone resorption. Paradoxically, most in vitro studies have suggested that glucocorticoids inhibit bone resorption but recently two groups have demonstrated increased osteolysis in glucocorticoid-treated bone organ cultures. The present study reexamines the effect of cortisol on basal bone resorption in neonatal mouse calvaria with particular emphasis on the effect of serum supplementation of the media. In the absence of serum, 45Ca release was significantly stimulated by 10(-7) M cortisol (treatment/control 1.37 +/- 0.06, P less than 0.005) and by 10(-6) M cortisol (treatment/control 1.27 +/- 0.08, P less than 0.005). The stimulation of resorption by 10(-7) M hydrocortisone was progressive from 24 to 96 hours of incubation. In contrast, when calvaria were incubated in the presence of 5% serum, bone resorption was not increased by cortisol (10(-8) M-10(-6) M). In the presence of 5% charcoal-stripped, heat-inactivated serum, there was a small stimulation of 45Ca release at 10(-6) M hydrocortisone only (treatment/control 1.19 +/- 0.06, P less than 0.01). Incubation of bones with indomethacin did not modify the effect of cortisol in either the presence or absence of serum. In serum-free conditions, cortisol 10(-8) M significantly inhibited the rate of thymidine incorporation, though at higher concentrations this effect was not seen. Cortisol produced a dose-related inhibition of serum-stimulated thymidine incorporation. It is concluded that the presence of serum substantially modifies the effect of cortisol on basal bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Lowe
C
C
Department of Medicine, University of Auckland, New Zealand.
Gray
D H
DH
Reid
I R
IR
D000818:Animals; D000831:Animals, Newborn; D001790:Blood Physiological Phenomena; D001862:Bone Resorption / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D012886:Skull / Q000378:metabolism*
D002118:Calcium; D006854:Hydrocortisone; D007213:Indomethacin