Metabolic studies in Cushing's syndrome

Glucocorticoids and sex-steroids can modulate osteogenesis in vivo and in vitro. Although the effects of glucocorticoids on bone cells in vitro have been described in detail, the role of sex-steroids is not as well defined. We examined whether sex-steroids influence bone metabolism indirectly by regulating glucocorticoid effects on bone. Interactions of the sex-steroid progesterone or its analog RU38486 with the glucocorticoid dexamethasone (dex) were studied in functional assays of osteogenesis. Three osteoblastic models were evaluated: (1) the rat bone marrow stromal cell (RBMC) nodule system; (2) the chick periosteal osteogenesis (CPO) model; and (3) ROS 17/2.8 cells. RU38486, progesterone, and unlabelled dex competitively inhibited 3H-dex uptake by ROS 17/2.8 cells as well as its (3H-dex) binding to cytosol preps. Both RU38486 and progesterone inhibited dex-induced increases in alkaline phosphatase in CPO cultures, in RBMC cultures, and in ROS 17/2.8 cells. Dex-induced decreases in cell proliferation in ROS 17/2.8 cells were reversed by RU38486 but dex-induced increases in proliferation in the CPO model were not affected. In CPO cultures, dex-induced increases in collagen synthesis were inhibited completely by RU38486 and progesterone. Dex-dependent nodule formation in the RBMC was blocked by RU38486. Both RU38486 and dex mediated reduction of calcium uptake in the CPO model but did not affect mineralized tissue area. The data indicate that RU38486 and progesterone competitively inhibit dex-mediated stimulation of osteogenesis in vitro; this inhibition is exerted on early but not late stage differentiation events of osteoprogenitor cells.

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Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss

Lukert

Johnson

Robinson

1992

Journal of Bone and Mineral Research

200

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This is a retrospective study of 15 postmenopausal or amenorrheic women aged 34-78 years who had taken prednisone for 6-108 months and were followed for 1 year while continuing to take doses of 5-15 mg/day. A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1). A group of 17 women, matched for age, were randomly selected from our computerized data base to serve as a control group (group 3), and 10 women of similar age who were taking ERT only (group 4) were selected to compare the response to ERT to that of group 2. Bone density (BD) was measured in the lumbar spine baseline and at 1 year using dual-photon or dual-energy x-ray absorptiometry. Spine density did not change significantly during the year of observation in group 1. Although BD decreased in 5 of 7 patients, the change was not significant (-0.034 +/- 0.018 g/cm2, p = 0.10). In group 2 BD increased significantly, with 7 of 8 patients showing an increase (0.037 +/- 0.011 g/cm2, p = 0.008). BD did not change significantly in the control group (0.013 +/- 0.008 g/cm2, p = 0.16). Loss of bone from the spine was significantly greater in group 1 than in controls (p = 0.02), but changes in group 2 were similar to those in the control group (p = 0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

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Metabolic studies in Cushing's syndrome

Cited by 7 publications

References 26 publications

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Clinical Studies With Acth and Cortisone in Renal Disease

Probing glucocorticoid‐dependent osteogenesis in rat and chick cells in vitro by specific blockade of osteoblastic differentiation with progesterone and RU38486

Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss

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