Pre-receptorial regulation of steroid hormones in bone cells: insights on glucocorticoid-induced osteoporosis.
In the past decades, concern on glucocorticoid-induced osteoporosis has increased with the widespread use of exogenous glucocorticoids (GC). Mature bone-forming cells (osteoblasts) are considered to be the principal site of action of GC in the skeleton. More likely, it is the entire cellular and molecular network surrounding these cells that is targeted by pharmacological doses of GC. Not only osteoblast and osteocyte metabolism, but the whole differentiation of mesenchymal stem cell toward the osteoblast lineage has been proven to be sensitive to GC. The effects of GC on this process are different according to the stage of differentiation of bone cell precursors. The presence of intact GC signalling is crucial for normal bone development and physiology, as opposed to the detrimental effect of high dose exposure. Both the physiological and pharmacological effects of GC are locally modulated by the activity of the 11beta-hydroxysteroid dehydrogenase 1 (HSD1) that acts primarily as a glucocorticoid activator converting the inactive glucocorticoid (cortisone) into the active hormone (cortisol). We reviewed the metabolic and differentiation pathways controlled by GC signalling. These data have been merged with the recent evidences that 11beta-HSD1 exert an important role by regulating the vulnerability of bone cells to GC. The different kinetics of 11beta-HSD1 at various stage of differentiation and the GC-dependency of enzymatic activity have been presented.
Pierotti
Silvia
S
Department of Medical Pathophysiology, University of Rome La Sapienza, Viale del Policlinico 155, Rome, Italy.
Gandini
Loredana
L
Lenzi
Andrea
A
Isidori
Andrea M
AM
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000502:physiology*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000502:physiology; D000328:Adult; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology* / Q000502:physiology*; D005938:Glucocorticoids / Q000009:adverse effects* / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced*
D005938:Glucocorticoids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2