Bone and mineral metabolism in the androgen-resistant (testicular feminized) male rat

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Abstract
Androgens have important effects on bone in vivo, possibly by direct activation of the androgen receptors in osteoblasts. To test this hypothesis, calcium homeostasis, bone mass, and bone turnover were evaluated in mature (4‐month‐old) androgen‐resistant (testicular feminized, TFM) male rats. Data were compared with data from both female and male littermates of the same age and strain. Compared to normal males, TFM had similar serum testosterone, twofold higher estradiol and estrone, and sixfold higher androstenedione concentrations. Compared to normal females, TFM rats showed lower estradiol but also elevated concentrations of androstenedione and estrone. Despite similar free 1,25‐(OH)2D3 concentrations, 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, were twofold higher in TFM rats than in females but not significantly different from males. Femoral length, diameter, and cortical thickness were intermediate between those of males and females. The cancellous bone density of the femur and cancellous bone volume of the proximal metaphysis of the tibia, however, were not significantly different between groups. The ash weight of the tibia was also not significantly different, and the ash weight of the four distal lumbar vertebrae ranged between 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 of TFM rats were in the female range and lower than in males. Bone formation and mineral apposition rates measured at the same site were intermediate between male and female rates. Bone formation rates were significantly higher in male than in female rats. We conclude that the absence of functional androgen receptors results in a decrease in radial and longitudinal bone growth and in a decrease in serum IGF‐I concentrations. TFM rats, however, have a cancellous bone volume and density similar to those of their normal male and female littermates. Bone turnover at the cancellous level is not increased compared to normal males. Cancellous bone volume in androgen resistance, in contrast to androgen deficiency, is probably maintained by a modest increase in serum estrogen concentrations.