Evidence From the Aged Orchidectomized Male Rat Model That 17β-Estradiol Is a More Effective Bone-Sparing and Anabolic Agent Than 5α-Dihydrotestosterone

Abstract

This study was designed to evaluate the impact of estrogen versus androgen action on orchidectomy (ORX)-induced bone loss and associated changes in body composition. During an experimental period of 4 months, aged (12-month-old) ORX rats were treated with 17␤-estradiol (E 2 ; 0.75 g/day) or different doses of the nonaromatizable androgen 5␣-dihydrotestosterone (DHT; 45, 75, and 150 g/day, respectively), via subcutaneous (sc) silastic implants. Low doses of DHT and E 2 inhibited the ORX-induced rise of bone turnover markers (serum osteocalcin and urinary deoxypyridinoline [DPD]) to a similar extent. High-dose DHT prevented the ORX-induced decrease of trabecular bone density but had no significant effect on cortical thinning as assessed by peripheral quantitative computed tomography (pQCT). This bone-sparing action of DHT occurred at the expense of hypertrophy of the ventral prostate and seminal vesicles. On the other hand, E 2 restored both trabecular bone density and cortical thickness in ORX rats and even prevented age-related bone loss. In contrast to DHT, E 2 increased lean body mass and inhibited the ORX-associated increase of fat mass, as measured by DXA. Administration of E 2 was associated with increased serum concentrations of insulin-like growth factor (IGF) I and decreased circulating levels of leptin. We conclude that, in the aged ORX rat model, E 2 is more effective in preventing ORX-induced bone loss than DHT. Additionally, E 2 has anabolic effects on muscle tissue and prevents the ORX-related increase of fat mass. Overall, these data suggest that androgen action on bone and body composition is dependent on stimulation of both androgen receptors (ARs) and estrogen receptors (ERs) .

Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men

“…In addition, this positive relationship was unrelated to the testosterone level as the association persisted after its adjustment ( Table 2). The role of estrogen receptor activation in the modulation of muscle mass remains unclear although some animal studies have revealed that estrogen receptor activation was involved in this process (32)(33)(34). Our results also revealed that total E 2 level, though positively related to muscle mass, was negatively related to muscle strength (Tables 2 and 4), in contrary to testosterone that was associated favorably with both muscle quantity and quality.…”

Serum estradiol is associated with lean mass in elderly Swedish men

“…In addition, there are indications that both ERa and ERb activation modulate muscle mass and/or function in mice (32,33). We also previously showed that E 2 , but not dihydrotestosterone, increased lean mass in orchidectomized, aged male rats (34). Finally, it is well established that estrogen treatment results in an anabolic effect on muscle mass in cattle (35).…”

“…Clinical trials investigating the effects of aromatase inhibition in older men showed no effect of the intervention on body composition or muscle strength (29,30) and, thus, did not support an important role of serum E 2 levels for lean mass in men. Nevertheless, animal studies have indicated that not only AR activation but also ER activation modulates lean mass (31)(32)(33)(34). It was recently demonstrated that ERa activation is required for normal muscle mass in male mice (31).…”

The COMT val158met Polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls

“…Estrogen has, in some previous studies, been shown to exert anabolic effects on muscle mass (47,48), suggesting that the effect on lean mass and muscle in COMT LL might also be a direct consequence of the elevated levels of estradiol.…”