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
