BONE AND MINERAL METABOLISM IN THE ANDROGEN-RESISTANT (TESTICULAR FEMINIZED) MALE-RAT

Androgens have important effects on bone in vivo, possibly by direct a ctivation of the androgen receptors in osteoblasts. To test this hypot hesis, calcium homeostasis, bone mass, and bone turnover were evaluate d in mature (4-month-old) androgen-resistant (testicular feminized, TF M) male rats. Data were compared with data from both female and male l ittermates of the same age and strain. Compared to normal males, TFM h ad similar serum testosterone, twofold higher estradiol and estrone, a nd sixfold higher androstenedione concentrations. Compared to normal f emales, TFM rats showed lower estradiol but also elevated concentratio ns of androstenedione and estrone. Despite similar free 1,25-(OH)2D3 c oncentrations, both TFM and male rats maintained higher serum calcium and phosphate concentrations than their female littermates. Serum IGF- I concentrations in TFM rats were decreased compared to male rats (-12 %) or female rats (-27%). Serum osteocalcin concentrations, however, w ere twofold higher in TFM rats than in females but not significantly d ifferent from males. Femoral length, diameter, and cortical thickness were intermediate between those of males and females. The cancellous b one density of the femur and cancellous bone volume of the proximal me taphysis of the tibia, however, were not significantly different betwe en groups. The ash weight of the tibia was also not significantly diff erent, and the ash weight of the four distal lumbar vertebrae ranged b etween male and female values. Bone mechanical properties as measured by torsional strength and energy absorption of the femur were lower in TFM than in females but not different from males. Osteoblast surfaces , osteoid, and osteoclast surfaces in the proximal tibial metaphysis o f TFM rats were in the female range and lower than in males. Bone form ation and mineral apposition rates measured at the same site were inte rmediate between male and female rates. Bone formation rates were sign ificantly higher in male than in female rats. We conclude that the abs ence of functional androgen receptors results in a decrease in radial and longitudinal bone growth and in a decrease in serum IGF-I concentr ations. TFM rats, however, have a cancellous bone volume and density s imilar to those of their normal male and female littermates. Bone turn over at the cancellous level is not increased compared to normal males . Cancellous bone volume in androgen resistance, in contrast to androg en deficiency, is probably maintained by a modest increase in serum es trogen concentrations.