In Vitro Effects of Growth Hormone on Cyclic AMP Metabolism in the Isolated Rat Diaphragm

Author(s):  
Jack L. Kostyo ◽  
Lynn P. Gimpel ◽  
Olle Isaksson
1967 ◽  
Vol 54 (4) ◽  
pp. 645-662 ◽  
Author(s):  
Å. Hjalmarson ◽  
K. Ahrén

ABSTRACT The effect of growth hormone (GH) in vitro on the rate of intracellular accumulation of the non-utilizable amino acid α-aminoisobutyric acid (AIB) was studied in the intact rat diaphragm preparation. Bovine or ovine GH (25 μg/ml incubation medium) markedly stimulated the accumulation of AIB-14C by diaphragms from hypophysectomized rats, while there was no or only a very slight effect on diaphragms from normal rats. In diaphragms from rats with the pituitary gland autotransplanted to the kidney capsule GH in vitro stimulated the accumulation of AIB-14C significantly more than in diaphragms from normal rats but significantly less than in diaphragms from hypophysectomized rats. Injections of GH intramuscularly for 4 days to hypophysectomized rats made the diaphragms from these rats less sensitive or completely insensitive to GH in vitro. These results indicate strongly that the relative insensitivity to GH in vitro of diaphragms from normal rats is due to the fact that the muscle tissues from these rats has been exposed to the endogenously secreted GH. The results show that GH can influence the accumulation of AIB-14C in the isolated rat diaphragm in two different ways giving an acute or »stimulatory« effect and a late or »inhibitory« effect, and that it seems to be a time-relationship between these two effects of the hormone.


Nature ◽  
1957 ◽  
Vol 179 (4557) ◽  
pp. 472-473 ◽  
Author(s):  
P. J. RANDLE ◽  
J. E. WHITNEY

1959 ◽  
Vol 18 (4) ◽  
pp. 395-408 ◽  
Author(s):  
K. L. MANCHESTER ◽  
P. J. RANDLE ◽  
F. G. YOUNG

SUMMARY 1. The effect of hypophysectomy, or of adrenalectomy, and injection of pituitary growth hormone (GH) or of cortisol, on the uptake of glucose and the incorporation of glycine into protein by isolated rat diaphragm, and the effect of the addition of insulin in vitro on these processes, has been studied. 2. Both hypophysectomy and adrenalectomy raised the uptake of glucose by isolated diaphragm, while treatment of the intact or of the hypophysectomized rat with GH, or of the intact or of the adrenalectomized rat with cortisol, depressed it. Although hypophysectomy and adrenalectomy did not influence the additional glucose uptake induced by 200 mu./ml. of insulin in vitro, both these operations enhanced the effect of 0·1–1·0 mu./ml. of insulin on glucose uptake by diaphragm in vitro. Treatment of the rat with GH or cortisol diminished the rise in glucose uptake of diaphragm induced by 0·1–1·0 mu./ml. insulin. 3. Hypophysectomy depressed, and administration of GH to the intact or hypophysectomized rat raised, the incorporation of glycine into protein of the isolated diaphragm, but neither of these operations altered the magnitude of the stimulation of incorporation induced by 1·0 mu./ml. insulin. 4. Adrenalectomy raised, and administration of cortisol to the intact or adrenalectomized rat depressed, the incorporation of glycine into protein of the isolated diaphragm; adrenalectomy enhanced, the injection of cortisol diminished, the effect of 1·0 mu./ml. insulin on these processes. 5. The possibility that GH directs insulin towards the stimulation of protein synthesis, in part by restraining the action of insulin on carbohydrate metabolism, is discussed.


1968 ◽  
Vol 57 (3_Suppl) ◽  
pp. S37-S48 ◽  
Author(s):  
Å. Hjalmarson

ABSTRACT Experiments were performed to study whether the influence of bovine growth hormone (GH) on the mebrane transport of labelled leucine and glycine in the isolated rat diaphragm was similar to that previously found for α-aminoisobutyric acid (Hjalmarson & Abrén 1967a, b). The relationship between the effects of GH on amino acid transport and protein synthesis was also studied. Addition of GH in vitro (25 μg/ml) to intact hemidiaphragms from hypophysectomized rats increased the accumulation of glycine in the intracellular water after 2 hours of incubation, while that of leucine was reduced. GH in vitro increased the incorporation rate into muscle protein of both glycine and leucine. An Intravenous (i. v.) injection of GH (10 μg) to hypophysectomized rats 60 min. before incubation increased the distribution ratio of leucine, while no significant effect was found on the incorporation into protein of this amino acid. On the other hand, an injection of GH (10 μg) 180 min. before incubation increased the in vitro incorporation of both leucine and glycine. This injection did not change the distribution ratio of glycine and that of leucine was significantly decreased. Repeated injections of GH (50 μg × 4 days) increased the incorporation of both glycine and leucine. This treatment also increased the accumulation of glycine after 2 hours of incubation, while no such effect was seen on the accumulation of leucine. In vitro addition of GH (25 μg/ml) did not significantly change the distribution ratio of glycine and leucine in diaphragms from hypophysectomized rats previously treated with GH. However, addition of GH in vitro to the diaphragms from these rats further increased the incorporation of glycine into protein. In addition, GH in vitro increased the accumulation of glycine also when the incorporation of this amino acid into protein was completely blocked by puromycin (500 μg/ml). The present results show that GH, at least in certain doses, may have a biphasic action on the membrane transport of normal amino acids. The results also indicate that GH may have separate effects on the membrane transport and the incorporation into protein of amino acids.


1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.


1968 ◽  
Vol 57 (3_Suppl) ◽  
pp. S19-S35 ◽  
Author(s):  
Å. Hjalmarson

ABSTRACT In vitro addition of bovine growth hormone (GH) to intact hemidiaphragms from hypophysectomized rats has previously been found to produce both an early stimulatory effect lasting for 2—3 hours and a subsequent late inhibitory effect during which the muscle is insensitive to further addition of GH (Hjalmarson 1968). These effects on the accumulation rate of α-aminoisobutyric acid (AIB) and D-xylose have been further studied. In presence of actinomycin D (20 μg/ml) or puromycin (100 μg/ml) the duration of the stimulatory effect of GH (25 μg/ml) was prolonged to last for at least 4—5 hours and the late inhibitory effect was prevented. Similar results were obtained when glucose-free incubation medium was used. Preincubation of the diaphragm at different glucose concentrations (0—5 mg/ml) for 3 hours did not change the GH sensitivity. Addition of insulin at start of incubation could not prevent GH from inducing its late inhibitory effect, while dexamethasone seemed to potentiate this effect of GH. Furthermore, adrenaline was found to decrease the uptake of AIB-14C and D-xylose-14C in the diaphragm, but not to change the sensitivity of the muscle to GH. Preincubation of the diaphragm for 3 hours with puromycin in a concentration of 200 μg/ml markedly decreased the subsequent basal uptake of both AIB-14C and D-xylose-14C, in the presence of puromycin, and abolished the stimulatory effect of GH on the accumulation of AIB-14C. However, the effect of GH on the accumulation of D-xylose-14C was unchanged. The present observations are discussed and evaluated in relation to various mechanisms of GH action proposed to explain the dual nature of the hormone.


1952 ◽  
Vol 197 (1) ◽  
pp. 151-166 ◽  
Author(s):  
C.R. Park ◽  
David H. Brown ◽  
Marvin. Cornblath ◽  
William H. Daughaday ◽  
M.E. Krahl

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