Effects of Cytochalasins on Several Actions of Growth Hormone on Muscle Metabolism

Summary

The different metabolic processes stimulated by growth hormone (GH) in diaphragm muscle from hypophysectomized rats may all be initiated by a common GH-sensitive event, or may be independent responses of muscle cells to GH. To assess these possibilities, cytochalasins were used to modify early events initiated by GH, and the influence of such modification on several responses to GH was compared. Diaphragm muscle was first exposed to cytochalasins, then to GH, and two responses to GH were measured simultaneously in each tissue. The same responses to GH were also measured in control tissues incubated without cytochalasins. Cytochalasin B alone (2 μg/ml) produced its typical suppression of the transport of the nonmetabolizable sugar, 3-O-methylglucose (3-OMG). Although GH (5 μg/ml) stimulated sugar transport in the presence of cytochalasin, B, the response to GH was significantly attenuated. However, in the same tissues, neither basal nor GH-stimulated incorporation of leucine into muscle protein was affected by cytochalasin B. When the stimulation by GH of the transport of the sugar, and of alpha-amino-isobutyric acid (AIB), a non-utilizable amino acid, were compared, only the sugar transport response was altered by cytochalasin B. However, this did not result merely from interference with the cellular capacity for sugar transport, since cytochalasin D also attenuated the stimulation of 3-OMG transport by GH without itself altering basal transport. The stimulation of leucine incorporation by GH was unaffected by cytochalasin D in the same tissues. Similarly, vinblastine (10^-5 M), a disrupter of microtubule structure, attenuated the stimulation of sugar transport by GH without affecting the stimulation of protein synthesis. Since one response to GH was consistently attenuated by agents which modify cell and membrane integrity, but two other responses to GH were unaffected in the same tissues, these findings suggest that the various actions of GH are independent early in the sequence of events by which GH stimulates muscle.

Key-Words:

Growth Hormone - Cytochalasins - Vinblastine - Sugar Transport - Protein Synthesis - Amino Acid Transport