Reduced Bone Mass and Muscle Strength in Male 5[alpha]-Reductase Type 1 Inactivated Mice

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. 5[alpha]-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5[alpha]-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5[alpha]-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5[alpha]-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 5[alpha]-reductase type 1 for bone mass using Srd5a1.sup.-/- mice. Four-month-old male Srd5a1.sup.-/- mice had reduced trabecular bone mineral density (-36%, p