Methods for identifying compounds for regulating muscle mass or function using corticotropin releasing factor receptors

A method for identifying candidate compounds for regulating skeletal muscle mass or function, comprising:

• (a) contacting a test compound with a cell expressing a functional CRF2R,
• (b) determining whether the test compound activates the CRF2R;
• and
• (c) identifying those test compounds which activate the CRF2R as candidate compounds for regulating skeletal muscle mass or function.

A method for identifying candidate compounds for regulating skeletal muscle mass or function comprising, in any order:

• (a) contacting a test compound with a cell expressing a functional CRF2R, and determining a level of activation of CRF2R resulting from the test compound;
• (b) contacting a test compound with a cell expressing a functional CRF1R, and determining the level of activation of CRF1R resulting from the test compound;
• followed by
• (c) comparing the level of CRF2R activation and the level of CRF1R activation;
• and
• (d) identifying those test compounds that show similar activity toward CRF2R and CRF1R or show selectivity for CRF2R as candidate compounds for regulating skeletal muscle mass or function.

A method for identifying candidate compounds that prolong or augment the agonist-induced activation of a CRF2R or of a CRF2R signal transduction pathway, comprising, in any order or concurrently:

• (a) contacting a test compound with a cell which expresses a functional CRF2R;
• (b) treating the cell with a CRF2R agonist for a sufficient time and at a sufficient concentration to cause desensitization of the CRF2R in control cells;
• followed by
• (c) determining the level of activation of the CRF2R;
• and
• (d) identifying those test compounds that prolong or augment the activation of a CRF2R or of a CRF2R signal transduction pathway as candidate compounds for regulating skeletal muscle mass or function.

A method for identifying candidate compounds for increasing CRF2R or CFR expression, comprising:

• (a) contacting a test compound with a cell or cell lysate containing a reporter gene operatively associated with a CRF2R regulatory element or a CRF regulatory element;
• (b) detecting expression of the reporter gene;
• and
• (c) identifying those test compounds that increase expression of the reporter gene as candidate compounds for regulating skeletal muscle mass or function.