MECHANISM OF MUSCLE PROTEIN LOSS IN MENOPAUSE

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DESCRIPTION (Adapted from the Applicant's Abstract): The long range goal is to understand the changes in protein metabolism that occur with menopause. Aging itself is marked with a decline in lean body or fat free mass (FFM) and a gain in fat mass. Menopause induces a further increased loss of FFM, largely from skeletal muscle. The key element to menopause is the loss of ovarian hormone production, which is treated by estrogen and progestin hormone replacement therapy (HRT). They hypothesize (I) that the loss of ovarian hormone production in menopause reduces protein synthesis in muscle, which increases loss of muscle mass over time and (ii) that HRT will attenuate this reduction in protein synthesis and muscle mass loss. To test this hypothesis, 40 women who have recently undergone menopause will be randomly assigned to HRT or placebo groups for 12 months. They will measure FFM and rates of protein synthesis and breakdown in these women upon entry and at the end of 12 months. They will measure FFM and skeletal mass by DEXA, total body water and urinary creatinine excretion. Protein synthesis and breakdown will be determined by infusing a non-radioactive 13C-labeled leucine tracer and blood, breath and muscle biopsy samples taken. Dilution of the tracer in blood will measure whole body protein synthesis and breakdown. Measurement of the leucine tracer into contractile muscle proteins (myosin heavy chain) will determine muscle protein synthesis. These measurements will provide new information on the possible mechanism that estrogen replacement via HRT regulates muscle protein and define whether HRT alters the decline in FFM loss after menopause, which translates over time into changes in FFM. Understanding the effect of HRT upon protein metabolism is important to the long-term health of postmenopausal women whose quality of life depends upon having adequate muscle mass and strength to be active and mobile with advancing years.