The Effect Of Exercise On The Phosphorylation of Progesterone Receptor In Skeletal Muscle

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Progesterone is a steroid hormone that is released from the ovaries, placenta and adrenal glands. Progesterone has many physiological effects on the body. In skeletal muscle it inhibits cell respiration, blocks glucose transporter 4 synthesis, and blocks glucose uptake. Opposite changes occur in skeletal muscle as a result of exercise. Phosphorylation of the progesterone receptor (PR) at Ser294 marks it for degradation, potentially blocking the action of progesterone. PURPOSE:To determine whether exercise leads to increased phosphorylation of the PR in skeletal muscle. METHODS: Male Sprague-Dawley rats were endurance- or interval-trained. Endurance training on treadmills was for either 4 days (n=6/group) or 53 days (n=6-7/group). Interval-trained rats trained identically to 53-day endurance-trained rats except that after 25 days high-intensity progressive interval training bouts were substituted for endurance bouts 3 times per week. White quadricep muscles from the rats were removed 20-24 hours post exercise for analysis. An acute muscle contraction bout was performed by stimulation of the sciatic nerve (STIM) in skeletal muscle-specific LKB1 knockout (KO; n=3) and littermate control (C; n=3) mice for 5 minutes (1 pulse/sec, 1 ms duration, 15V). Gastrocnemius muscles were removed immediately post-stimulation for analysis. Muscles were homogenized and analyzed by electrophoresis and western blotting for total PR and PR phosphorylation at Ser294. RESULTS: 4 day endurance training increased phosphorylation of PR in white quadriceps by 207%. PR phosphorylation was increased in white quadriceps of both 53-day endurance (69% increase) and interval trained (110% increase) rats. Total PR was not affected by either 53-day training bout. Acute STIM in C mice resulted in a 212% increase in PR phosphorylation, but no increase was observed in mLKB1-KO mice. CONCLUSIONS: Exercise and muscle contraction leads to increased skeletal muscle PR phosphorylation in an LKB1 dependent manner. However, this phosphorylation event does not lead to decreased PR levels, at least after 53 days of training. Thus, further work will be required to characterize any functional consequence of exercise on progesterone signaling in skeletal muscle. This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR-051928.