| First Author | Windahl SH | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 6 | Pages | e21402 |
| PubMed ID | 21731732 | Mgi Jnum | J:174355 |
| Mgi Id | MGI:5085925 | Doi | 10.1371/journal.pone.0021402 |
| Citation | Windahl SH, et al. (2011) Reduced bone mass and muscle strength in male 5alpha-reductase type 1 inactivated mice. PLoS One 6(6):e21402 |
| abstractText | Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5alpha-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5alpha-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5alpha-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5alpha-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5alpha-reductase type 1 for bone mass using Srd5a1(-/-) mice. Four-month-old male Srd5a1(-/-) mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1(-/-) mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1(-/-) mice. Male Srd5a1(-/-) mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1(-/-) mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5alpha-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5alpha-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1(-/-) mice, is an indirect effect mediated by elevated circulating androgen levels. |
