Endocrinology, Vol 112, 931-939, Copyright © 1983 by Endocrine Society

ARTICLES

Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae

E Canalis

Glucocorticoid-induced osteoporosis is believed to be caused by increased bone resorption and decreased bone formation. However, the direct effects of glucocorticoids on bone formation are, as yet, not fully understood. Cortisol, corticosterone, and dexamethasone were examined for their effects on alkaline phosphatase activity, the incorporation of [3H]proline into type I collagen, DNA content, and mitotic index in intact 21-day-old fetal rat calvariae. After 24 h of treatment, cortisol at 1-100 nM increased the incorporation of [3H]proline into type I collagen, whereas at 1-10 microM, cortisol inhibited type I collagen labeling. After 96 h, cortisol (0.1-10 microM) had an inhibitory effect on type I collagen labeling and alkaline phosphatase activity. Cortisol had a small, not dose dependent, and transient stimulatory effect on alkaline phosphatase which appeared after 12-24 h of exposure, whereas the inhibitory effect was dose related, it appeared and was near-maximal after 48 h of continuous treatment with cortisol. Corticosterone and dexamethasone had an effect similar to that of cortisol on type I collagen synthesis and alkaline phosphatase activity. None of the steroids tested affected the release of the enzyme into the culture medium. Cortisol, corticosterone, and dexamethasone did not alter calvarial DNA content after 24 h of treatment, but after 96, concentrations of 1 nM to 10 microM were inhibitory. The decrease in DNA appeared after 48 h of exposure to 100 nM cortisol and was maximal after 72 h. Histological sections showed a marked and generalized decrease in the number of mitoses after colcemid arrest in calvariae treated with 100 nM cortisol, corticosterone, or dexamethasone for 96 h. These studies indicate that glucocorticoids have a dual effect on type I collagen synthesis and alkaline phosphatase activity in cultured calvariae: a transient stimulatory effect after short term treatment and an inhibitory one after long term exposure. The latter is related to a generalized decrease in cell population.

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