Androgens and their effects on bone and body composition: lessons from an aged male rat model.
Dirk Vanderschueren, Liesbeth Vandenput, Eric Van Herck, Johannes Swinnen, Steven Boonen and Roger Bouillon
LEGENDO, KUL, Belgium
Aging men lose both bone and muscle tissue and gain fat mass.
In an aged orchidectomized male rat model, testosterone (T) prevents both bone loss and decrease of lean body mass.
These bone sparing effects of testosterone are already apparent following administration of relatively a low dose of T ( which only partially prevent loss of prostate and seminale vesicles ) Interestingly, T action on lean body mass correlates significantly with its effects on bone mineral.
It is unknown however to which extent this important aspect of androgen action depends on stimulation of androgen (AR) or on one or both estrogen receptors(ER).
In order to further explore this aspect of androgen action , different doses of the nonaromatisable androgen DHT ( this androgen stimulates only the AR) were tested in the same model. Its action was compared with the effects of estradiol ( E2.) ( T may not only be transformed into E2 via aromatisation but recent studies of our and other groups show that at least part of its bone sparing effects depend on one or both of the ER).
These studies have shown:
1.that even very high doses of DHT ( resulting in hypertrophy of prostate and seminal vesicles ) are not able to either prevent loss of lean body mass or increase of fat. The highest dose of DHT showed some bone sparing effect, but only on trabecular and not on cortical bone.( It is unknown to which extent this relates to its lack of effect on lean body mass) . In this context , the observation of an inhibitory efect of DHT on serum IGF-I.may be relevant.
2. that E2 prevents the increase of fat in this model, presumably via its inhibitory effect on leptin. E2 also stimulates lean body mass. Clear bone sparing effects of E2 were again demonstrated at both the cortical and cancellous bone compartiments. Such E2 action was observed with lower doses than reported previously and was associated with increases of serum IGF-I.
In conclusion:
T is the most effective androgen with respect to fat, bone and lean body mass in an aged male rat . Its superiority is probably explained by its ability to be aromatized and to stimulate one or both ER. receptors. This aspect of its action may explain part of its bone sparing effect and fully explain its inhibitory action on fat.
However, its AR stimulatory action (as shown in the DHT experiments) may provide an additional benefit to ( trabecular ) bone.
T and E2 , in contrast with DHT, stimulate lean body mass. The latter effect of T may contribute to its superiority as a bone sparing hormone.
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