Regulation of Melanocyte Stimulating Hormone Action at the Receptor Level: Discontinuous Binding of Hormone to Synchronized Mouse Melanoma Cells During the Cell Cycle

Melanocyte stimulating hormone coupled to Sepharose effects an increase in tryosinase (EC 1.14.18.1; monophenol monoxygenase) activity of cultivated mouse melanoma cells. Synchronized cells are found to respond to melanocyte stimulating hormone only in the G2 phase of the cell cycle, although their response to cyclic AMP is independent of position in the cell cycle. The binding of (125)I-labeled melanocyte stimulating hormone occurs predominantly in G2. These observations are satisfied by a model in which the hormone can activate adenylate cyclase (EC 4.6.1.1) by binding to a melanocyte stimulating hormone receptor only in G2; the events distal to cyclic AMP production can occur throughout the cell cycle.