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The acute effects of growth hormone on the oxidation of [1-14C]-pyruvate to 14CO2 were studied in epididymal adipose tissue obtained from hypophysectomized rats. At concentrations ranging from 10 ng/ml to 1 microgram/ml, growth hormone increased the rate of pyruvate oxidation by 20-60%. A lag period of up to 30 min was required for the full effect of the hormone to develop. Addition of fructose to the incubation medium increased the rate of pyruvate oxidation in response to either growth hormone or insulin. The effects of 1 microgram/ml growth hormone were comparable in magnitude to those of 1 mU/ml insulin, and pyruvate oxidation in the presence of both agents was no greater than in the presence of either on its own. The enhancement of pyruvate oxidation by growth hormone, like that caused by insulin, probably results from activation of pyruvate dehydrogenase. Increased activity of pyruvate dehydrogenase was found in cell-free extracts of adipose tissue that had been exposed to either growth hormone or insulin. The response of tissue segments to growth hormone followed the same pattern as observed for other acute insulin-like effects of the hormones; it was transient and disappeared within 3 hours despite continued presence of the hormone. Previous exposure of the tissues to growth hormone made them refractory to the hormone upon reexposure.

Epididymal fat incubated in the presence of glucose and dl-leucine-2-C14 incorporated C14 into fatty acids and CO2. Insulin at physiological concentrations increased leucine uptake and conversion to fatty acids and usually decreased oxidation to C14O2. In the absence of glucose, lipogenesis was sharply curtailed, but oxidation of leucine to C14O2 was unchanged. In this situation, insulin failed to increase lipogenesis from leucine, although its stimulatory action on leucine uptake remained. Virtually all the leucine C14 taken up under the influence of insulin now appeared as C14O2. Insulin similarly increased the uptake and conversion of acetate-2-C14 to fatty acids and decreased C14O2 production in the presence of glucose but not in its absence. Addition of α-aminoisobutyric acid to the medium blocked the stimulatory effect of insulin on leucine uptake. From these observations it is suggested that insulin may affect the synthesis of fatty acids from leucine in two ways: directly by increasing the transport of leucine into the cell and indirectly by increasing the availability of glucose and hence channeling the acetate derived from leucine into fatty acids.

In its initial encounter with growth hormone (GH) in vitro, epididymal fat excised from GH-deficient rats responds with an insulin-like increase in glucose metabolism. Tissues freshly excised from normal rats are refractory to the insulin-like effects of GH, but become sensitive immediately after surgical stress. Reversal of refractoriness is prevented by administration of the opioid antagonist, naloxone, just prior to stress, suggesting a possible role of beta-endorphin or related peptides. These experiments were undertaken to determine the source of these peptides which might equally well be released from the pituitary, adrenal medullae, or nerve endings in response to stress. Since adrenalectomy, like stress, also results in increased secretion of adrenocorticotropic hormone (ACTH) and related peptides, we studied the effects of GH on glucose oxidation in adipose tissue obtained from adrenalectomized rats and found a significant insulin-like response to GH in tissues studied 4 days after adrenalectomy. This effect was not due to GH deficiency, since plasma concentrations were only slightly reduced by adrenalectomy. Administration of naloxone (250 micrograms/rat), 30 or 60 min before sacrifice, or dexamethasone (100 micrograms/injection), 60 and 120 min before sacrifice, prevented a response to GH without affecting circulating levels of GH. The effects of adrenalectomy could not be reproduced by preincubation of adipose tissue from normal nonstressed rats with ACTH and beta-endorphin, but were duplicated by preincubation of adipose tissue for 15 min in medium in which pituitary glands had previously incubated in the presence of corticotropin-releasing hormone (0.1 microM) and arginine vasopressin (0.2 microM). Addition of naloxone (250 micrograms/ml) blocked this effect.(ABSTRACT TRUNCATED AT 250 WORDS)