Evidence from the aged orchidectomized male rat model that 17beta-estradiol is a more effective bone-sparing and anabolic agent than 5alpha-dihydrotestosterone.
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 17beta-estradiol (E2; 0.75 microg/day) or different doses of the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT; 45, 75, and 150 microg/day, respectively), via subcutaneous (sc) silastic implants. Low doses of DHT and E2 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, E2 restored both trabecular bone density and cortical thickness in ORX rats and even prevented age-related bone loss. In contrast to DHT, E2 increased lean body mass and inhibited the ORX-associated increase of fat mass, as measured by DXA. Administration of E2 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, E2 is more effective in preventing ORX-induced bone loss than DHT. Additionally, E2 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).
Vandenput
L
L
Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Belgium.
Boonen
S
S
Van Herck
E
E
Swinnen
J V
JV
Bouillon
R
R
Vanderschueren
D
D
D000375:Aging / Q000502:physiology; D045930:Anabolic Agents / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D009919:Orchiectomy; D010024:Osteoporosis / Q000188:drug therapy*; D051381:Rats
D045930:Anabolic Agents; D013196:Dihydrotestosterone; D004958:Estradiol