Cortisol mobilizes mineral stores from vertebral skeleton in the European eel: an ancestral origin for glucocorticoid-induced osteoporosis?

International audience; Endogenous cortisol excess and glucocorticoid (GC) therapy are a major cause for secondary osteoporosis in humans. Intense bone resorption can also be observed in other vertebrates such as migratory teleost fish at the time of reproductive migration and during fasting when large amounts of calcium and phosphate are required. Using a primitive teleost, the European eel, as a model, we investigated whether cortisol could play an ancestral role in the induction of vertebral skeleton demineralisation. Different histological and histomorphometric methods were performed on vertebral samples of control and cortisol-treated eels. We demonstrated that cortisol induced a significant bone demineralisation of eel vertebrae, as shown by significant decreases of the mineral ratio measured by incineration, and of the mineralisation degree measured by quantitative microradiography of vertebral sections. Histology and image analysis of ultrathin microradiographs showed the induction by cortisol of different mechanisms of bone resorption, including periosteocytic osteolysis and osteoclastic resorption. Specificity of cortisol action was investigated by comparison with the effects of sex steroids. Whereas testosterone had no effect, estradiol induced vertebral skeleton demineralisation, an effect related to the stimulated synthesis of vitellogenin, an oviparous specific phospho-calcio-lipoprotein. In contrast, cortisol demineralisation effect was not related to any stimulation of vitellogenin. This study demonstrates GC-induced bone demineralisation in an adult non-mammalian vertebrate, which undergoes natural bone resorption during its life cycle. Our data suggest that the stimulatory action of cortisol on bone loss may represent an ancestral and conserved endocrine regulation in vertebrates.