Cortisone-induced osteoporosis: effects on bone adenylate cyclase.
Glucocorticoid excess results in osteoporosis by inhibiting bone formation as well as by increasing bone resorption. The cellular mechanism for the glucocorticoid effect is unknown but has been postulated to be due to enhancement of the cyclic AMP response to PTH. This study examined the effect of in vivo administration of a glucocorticoid on adenylate cyclase activity in plasma membranes isolated from mineralized bone. Glucocorticoid excess was induced by implanting cortisone subcutaneously in adult female guinea pigs. At the end of 3 weeks skeletal plasma membranes were obtained, and adenylate cyclase activity was compared with that of normal age-matched guinea pigs. The specific activity of basal adenylate cyclase activity was significantly greater in the cortisone-treated animals (77.7 +/- 10 vs. 41.9 +/- 4.4 pmol cAMP/mg protein/15 min, p < 0.005), but PTH stimulated both to an equal degree. In contrast to the increased specific activity of intact adenylate cyclase, the specific activity of the catalytic unit was lower in the membranes from cortisone-treated animals. We also examined the effect of cortisone treatment on the modulation of adenylate cyclase by divalent cations. Neither the KaMg or the ability of Ca2+ to inhibit enzyme activity was found to differ between normal and cortisone-treated animals. In addition, PTH caused an increase in Mg2+ affinity in both sets of membranes to a comparable degree. The effect of cortisone could not be attributed to altered amounts of Ni present in these membranes; we were unable to satisfactorily quantitate the amounts of Ns.(ABSTRACT TRUNCATED AT 250 WORDS)
University of Southern California School of Medicine, Los Angeles 90033.
R K
RK
Rude
H E
HE
Gruber
S B
SB
Oldham
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001842:Bone and Bones / Q000201:enzymology* / Q000473:pathology; D002118:Calcium / Q000494:pharmacology; D003348:Cortisone / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006168:Guinea Pigs; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced*; D010281:Parathyroid Hormone / Q000494:pharmacology
D010281:Parathyroid Hormone; D008345:Manganese; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium; D002118:Calcium; D003348:Cortisone