1.Effect of 11β-HSD1 dehydrogenase activity on bone histomorphometry of glucocorticoid-induced osteoporotic male Sprague-Dawley rats.
M R Elvy SUHANA ; H S FARIHAH ; O FAIZAH ; A S NAZRUN ; M NORAZLINA ; M NORLIZA ; S IMA-NIRWANA
Singapore medical journal 2011;52(11):786-793
INTRODUCTIONGlucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, which plays an important role in regulating corticosteroids. 11β-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11β-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoid-induced osteoporotic bone in rats.
METHODSA total of 30 male Sprague-Dawley rats (aged three months, weighing 200-250 g) were divided into three groups of ten each. Group 1 rats were the baseline control, which were sacrificed untreated at the beginning of the study. Group 2 rats underwent sham operation and were administered with vehicle olive oil intramuscularly at 0.05 ml/kg. Group 3 rats were adrenalectomised and administered with an intramuscular injection of dexamethasone 120 μg/kg body weight/day. The treatment was started two weeks after the operation, for a duration of two months. Plasma osteocalcin, plasma pyrodinoline, plasma corticosterone and 11β-HSD1 were measured, and bone histomorphometry analysis was performed.
RESULTSDexamethasone treatment caused an increase in plasma corticosterone level, together with a significant reduction in 11β-HSD1 dehydrogenase activity of the bone, along with a higher plasma level of the bone resorption marker, pyridinoline. Dexamethasone treatment also caused a reduction in trabecular volume, number and thickness, and an increase in trabecular separation.
CONCLUSIONLong-term glucocorticoid treatment reduces the 11β-HSD1 dehydrogenase activity in the bone, which can otherwise lead to bone loss due to the increased level of active glucocorticoids.
11-beta-Hydroxysteroid Dehydrogenase Type 1 ; metabolism ; Adrenal Cortex Hormones ; metabolism ; Amino Acids ; pharmacology ; Animals ; Body Weight ; Bone and Bones ; metabolism ; Corticosterone ; blood ; Dexamethasone ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; methods ; Gene Expression Regulation, Enzymologic ; Glucocorticoids ; metabolism ; Humans ; Male ; Osteoporosis ; metabolism ; Rats ; Rats, Sprague-Dawley