Evaluation of the effect of thyroid hormone on the bone structure and physiology of mice with the gene inactivation of α2C-adrenoceptor.

Author(s)

Marilia Bianca Cruz Grecco Teixeira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2015-09-22

Examining board members

Cecilia Helena de Azevedo Gouveia Ferreira; Charles Heldan de Moura Castro; Julio Cesar Batista Ferreira; Katiucia Batista da Silva Paiva; Bruno Ferraz de Souza

• Advisor: Cecilia Helena de Azevedo Gouveia Ferreira

Abstract

Data demonstrates that sympathetic nervous system (SNS) activation causes osteopenia via β2-adrenoceptor signaling. A recent study showed that mice with gene inactivation of the adrenergic receptor α2A and α2C (α2A/α2C-AR-/-) have a high bone mass phenotype, even presenting SNS hyperactivity. Also, these knockout (KO) mice are resistant to the thyroid hormone-induced osteopenia. These findings suggest that SNS interacts with thyroid hormone (TH) to regulate bone mass and α2A and/or α2C adrenoceptors may have an important role in mediating the actions of the SNS in the skeleton. In this study, we had the following objectives: (i) to evaluate whether the isolated inactivation of α2CAR interferes with the bone metabolism and to evaluate whether the action of HT on bone tissue depends on α2CAR, treated with 20 times the physiological dose of T3. The microtomography analysis showed that the trabecular bone volume of the femur and of the sixth lumbar vertebra (L6) were, respectively, lower and higher in α2C-AR-/- mice, when compared with WT animals. Furthermore, we showed a resistance of KO animals on the deleterious effects of TH on bone. These findings suggest: (i) α2C-AR is involved with bone longitudinal growth; (ii) α2C-AR may mediates the effects of the SNS in the bone in a skeletal site specific manner, (iii) the actions of thyroid hormone on bone metabolism involves interactions with the SNS via α2C adrenergic receptors. (AU)