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Evidence From the Aged Orchidectomized Male Rat Model That 17β‐Estradiol Is a More Effective Bone‐Sparing and Anabolic Agent Than 5α‐Dihydrotestosterone
Author(s) -
Vandenput L.,
Boonen S.,
Van Herck E.,
Swinnen J. V.,
Bouillon R.,
Vanderschueren D.
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.11.2080
Subject(s) - endocrinology , medicine , deoxypyridinoline , dihydrotestosterone , androgen , cortical bone , estrogen , testosterone (patch) , quantitative computed tomography , anabolism , osteocalcin , levator ani , muscle hypertrophy , bone remodeling , bone density , chemistry , osteoporosis , anatomy , alkaline phosphatase , hormone , pelvic floor , biochemistry , enzyme
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 17β‐estradiol (E 2 ; 0.75 μg/day) or different doses of the nonaromatizable androgen 5α‐dihydrotestosterone (DHT; 45, 75, and 150 μg/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).