Studies on the effect of anterior-pituitary growth hormone on oxidative phosphorylation in rat-liver mitochondria

Injection of anterior-pituitary growth hormone into the intact rat causes changes of metabolLsm leading to a greater oxidation of fat (Young, 1945;Greenbaum & McLean, 1953) and a sparing of protein (Young, 1945;Li, Simpson & Evans, 1948).The mechanism whereby these changes are effected is unknown.The diverse nature of the metabolic changes induced by the action of the hormone make it seem unlikely that they could all arise as the result of the modification of a single specific enzyme and it appeared more profitable to investigate the possibility that the effects are mediated by some primary change of a more general character.The change could involve (i) an effect on the permeability of the cell wall itself [as has been suggested by Kipnis & Cori (1957) for the action of insulin] or on the membrane of the subcellular structures [as has been suggested by Tapley & Cooper (1956) for the action of thyroxin], or (ii) the action could be on an ubiquitous system such as oxidative phosphorylation which could modify energy relationships within the cell.Park, Meriwether & Park (1958) have suggested that thyroxine acts directly on the enzyme system carrying out oxidative phosphorylation.In the experiments reported here it has been shown that growth hormone uncouples phosphorylation when D(-)-fl-hydroxybutyrate was oxidized by rat-liver mitochondria.(Throughout this paper the lowered efficiency of oxidative phosphorylation is referred to as an 'uncoupling' for the sake of brevity, although it is realized that the effect described here is not that usually implied by the use of this term.The efficiency here seems to be lowered not by any reduction in the rate of phos- phorylation but by the appearance of additional oxidation.)It has also been shown that growth hormone in very low concentration causes striking changes in mitochondrial permeability.