title: Effect of 11β-HSD1 dehydrogenase activity on bone histomorphometry of glucocorticoid-induced osteoporotic male Sprague-Dawley rats.
abstract: BACKGROUND
  Glucocorticoids 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Dexamethasone 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.
  
  
  CONCLUSIONS
  Long-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.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
authors.forename: M R
authors.initials: MR
authors.lastname: Elvy Suhana
authors.forename: H S
authors.initials: HS
authors.lastname: Farihah
authors.forename: O
authors.initials: O
authors.lastname: Faizah
authors.forename: A S
authors.initials: AS
authors.lastname: Nazrun
authors.forename: M
authors.initials: M
authors.lastname: Norazlina
authors.forename: M
authors.initials: M
authors.lastname: Norliza
authors.forename: S
authors.initials: S
authors.lastname: Ima-Nirwana
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000305:Adrenal Cortex Hormones; D000596:Amino Acids; D005938:Glucocorticoids; C015484:pyridinoline; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003345:Corticosterone