Growth hormone stimulation of amino acid transport into rat tissues in vivo.

The transport of free amino acids into cells is the first step in protein synthesis, and, therefore, an essential part of growth. Hormones that increase protein synthesis and growth over a period of time can do so only if increased supplies of free amino acids are made available inside the cells. This increased supply may occur (a) through an increased formation of amino acids within the cells; (a) through their increased active transport into the cells; or, (c) through a decreased removal of amino acids by catabolism. For tissues with relatively little amino acid metabolism, (a) and (e) would play minor roles; for all tissues, the “essential” amino acids would still have to be supplied externally. Growth hormone has long been known to decrease plasma free amino acid levels (2, 3). This decrease could arise from an increased uptake of amino acids by cells, but could not readily result from decreased cell amino acid catabolism. The increased uptake could, on the one hand, be the cause of increased protein synthesis, the latter resulting from the increased cell amino acid levels, or it could be the result of a primary increase in protein synthesis, which would deplete cell amino acids and accelerate entrance indirectly. In the former case, increased cell levels of free amino acids would be expected, whereas in the latter they would be decreased unless the transport process was geared to respond directly to primary changes in protein synthesis. Indirect evidence has suggested that cell amino acids must be increased under growth hormone action, since the total body nitrogen pool rises while the plasma level falls (4). Recently, we reported that bovine growth hormone increased the uptake of the nonmetabolieable amino acid, a-aminoisobutyric acid, by several tissues in normal rats (5). This amino acid is transported into cells in a manner similar to the neutral naturally occurring amino acids (6, 7), undergoing competition with normal amino acids in all cases examined.1 Its chemical structure appears not to be altered in the rat (5, 7) or human body (7). By its use, the transport process can be isolated and studied independently of possible actions of the hormone on amino acid synthesis or degradation. Any such alterations would, of course, obscure effects on transport alone. Changes in a-aminoisobutyric acid distribution after growth hormone administration are therefore taken to mean a change in amino acid transport into cells (5).