Influence of sex and 17-B-estradiol on metabolism and inflammation in skeletal muscle

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1. Men and women use different fuels during endurance exercise with women burning more fat and less carbohydrate and protein as compared with men.  By giving estrogen (the female sex hormone) supplements to men, we found that they had a similar metabolic profile to that seen in women during exercise.  We have started to characterize these estrogen effects at the level of the muscle cell using biochemical and molecular analyses and would like to further characterize these effects using powerful methods of entire genome profiling (gene chips).  We will also use trangenic animals lacking the estrogen receptor to determine what role the cell receptor has in mediating the metabolic effects.  2. After very strenuous exercise (eccentric) there is muscle damage and inflammation.  In spite of similar damage, women have a lesser inflammatory response, yet we do not know the mechanism behind this observation.  It is possible that estrogen functions as an anti-oxidant directly or through interactions with receptors on the muscle to alter cellular processes that protect the cell from the damaging effects of this type of muscle contraction.  We would like to use our model of estrogen administration to men and the gene chip experiments in men and women to characterize the response in muscle after damaging exercise.  Overall, we feel that estrogen will make muscles more metabolically efficent during exercise and lessen some of the effects of damaging exercise.