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Biomedical subjects

K Albertsson-Wikland

Publications and source records attributed to K Albertsson-Wikland.

154 records · Page 9Linked to original sources

Relationship between the biological and immunological activities of growth hormone circulating in normal rats.

The ability of GH to induce refractoriness to its own insulin-like effect in adipose tissue is highly specific for GH. Moreover, refractoriness to the insulin-like action of GH can be induced with low concentrations of GH in the range of 10 ng/ml. In the present study, the ability of plasma from normal rats to induce refractoriness to the effect of GH on the production of 14CO2 from [14C]glucose in epididymal fat pads from hypophysectomized rats was examined as a measure of a GH-specific biological effect of the plasma. Plasma levels of GH were measured by RIA. Without exception, preincubation of fat pads with plasma having immunoreactive rat GH (rGH) levels over 50 ng/ml induced refractoriness to GH, whereas plasma having immunoreactive rGH levels below 15 ng/ml did not exert this effect. In fat pads preincubated with plasma having immunoreactive rGH levels between 10-50 ng/ml, the effect of a second exposure to GH varied in a dose-dependent manner. Also, plasma pools that were diluted with buffer or plasma from hypophysectomized rats were unable to induce refractoriness when the calculated or measured levels of immunoreactive rGH were below 15 ng/ml. The results suggest that in terms of the ability of GH to induce refractoriness to the insulin-like effect of the hormone, a very good correlation exists between the biological and immunological activities of GH in plasma from normal undisturbed rats.

Adipose Tissue↗

Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats.

The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats. Replacement therapy with 3 different doses of human GH [(hGH) Crescormone] was started 10-14 days after hypophysectomy and was continued for 5 days. Longitudinal bone growth, as measured by the tetracycline method, and body weight were determined during the injection period. With a daily replacement dose of 128 micrograms of hGH body weight gain and longitudinal bone growth were significantly higher when the hormone was injected 4 and 8 times per day compared with animals receiving the hormone in one daily injection. When the dose of hGH was 32 or 8 micrograms per day, longitudinal bone growth and body weight gain were more pronounced in animals receiving the hormone 2 and 4 times per day compared with animals receiving the hormone one or 8 times per day. The results of the present study demonstrate that the frequency of GH administration influence body growth. The findings suggest that the secretory pattern of GH influence the growth rate under in vivo condition.

Animals↗

Inhibition of adenylate cyclase activity in muscles by growth hormone.

The acute effects of GH have a characteristic lag period of 10-30 min before a short lasting stimulation is seen, suggesting that some metabolic events precede the observable stimulation. There is evidence that cyclic nucleotides are involved in the mechanism of action of GH, which this work attempts to evaluate further. The effect of GH (rat, bovine, and human) on adenylate cyclase activity was measured in diaphragms and hearts of young normal and hypophysectomized rats. Measurements were made both after short term in vivo treatment and after addition directly to isolated muscle membranes. The muscles were homogenized and centrifuges, and the adenylate cyclase activity in the pellet was assayed. The injection of 4.5-450 pmol GH, iv, induced, within 3 min, inhibition of basal as well as epinephrine-stimulated adenylate cyclase activities, in both the absence and presence of a GTP analog, in the tissues studied. When added directly to the muscle membranes in the adenylate cyclase assay, 0.45-45 nM GH caused a dose-dependent inhibition of the adenylate cyclase activity, but only in the presence of a GTP analog. These findings clearly demonstrate that a physiological dose of GH has a rapid and direct inhibitory effect on muscle membrane adenylate cyclase, well within the lag period of the anabolic effect of the hormone.

Adenylyl Cyclase Inhibitors↗

Circumstantial evidence for a role of the secretory pattern of growth hormone in control of body growth.

The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats which were given replacement therapy with corticosteroids, thyroxine and GH with start of therapy on the day of surgery. Longitudinal bone growth, as determined by the tetracycline method, was measured during the last 5 days of the 9 day long period with replacement therapy. The daily replacement dose of GH (bGH-17:NIH) was 200 micrograms and was given on 1, 2, 4 or 8 occasions. Longitudinal bone growth was enhanced in the groups of animals receiving the hormone on two or more occasions per day. The most pronounced response was seen with an administration frequency of four times per day. Changes in body weight during the injection period showed similar changes. The results of the present study show that the administration frequency of growth hormone is important for the growth rate in hypophysectomized rats which have been given replacement therapy. The findings suggest that the secretory pattern of GH is an important factor for optimum growth.

Animals↗

Plasma levels of growth hormone in female rats of different ages.

Radioimmunoassayable growth hormone (GH) was determined in fed and fasted female rats of different ages. In 6-40 day-old rats blood was collected at hourly intervals in groups of rats at different time intervals during the day. Within each age group the variation in plasma GH was considerable. In 6-14 day-old rats plasma GH was generally elevated. By day 18 levels declined, lowest on day 22 and by day 26 again increasing. In 14 day-old rats the median plasma level of GH was 22 ng/ml, in 22 day-old rats less than 5 ng/ml and in 40 day-old rats 43 ng/ml. In 14 day-old rats levels ranged from less than 5 ng/ml--148 ng/ml, in 22 day-old rats from less than 5 ng/ml--34 ng/ml and in 40 day-old rats from less than 5 ng/ml--greater than 200 ng/ml. A 20 h fasting period was associated with a significant decrease in plasma GH. In 45 day-old rats, the variations in plasma GH of individual animals were studied by obtaining sequential blood samples from unrestrained, undisturbed animals with implanted intra-aortic cannulae. In these rats GH secretion was characterized by an episodic release, occurring every 2--4 h. After a 20 h fasting period major peaks were depressed and occurred less frequently. It is concluded that there is an age-related as well as a circadian rhythm in growth hormone secretion in the rat and that sequential sampling of blood is essential for the evaluation of the secretory pattern.

Aging↗

Effect of insulin and adrenaline on cyclic AMP in the diaphragm of normal and diabetic rats.

The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.

Animals↗

Development of responsiveness of young normal rats to growth hormone.

Growth hormone (GH) exerts a biphasic effect on the membrane transport of amino acids and sugars in diaphragms from hypophysectomized rats. A stimulatory (insulin-like) effect of GH is observed for approximately 3 hr after the administration of the hormone, and then the diaphragm becomes "refractory" to further administration of the hormone for 24-48 hr. In the present study the in vitro responsiveness of diaphragms from young normal rats of different ages to bovine growth hormone (bGH) was studied by measuring the accumulation of alpha-aminoisobutyric acid (AIB), cycloleucine, and 3-0-methyl-glucose (3-OMG) and by determining the incorporation of phenylalanine into diaphragm proteins. bGH increased the uptake of AIB in 6, 10, 14, 18, and 22-day old and of cycloleucine in 10, 14, and 18-day old rats, respectively. The maximal stimulatory effect was seen in 18-day old rats and no effects were seen in 26 and 30-day old animals. A similar pattern of age-related responsiveness was also seen when the uptake of 3-OMG and the incorporation of phenylalanine were studied. The rate of accumulation of the nonutilizable amino acids, as well as the rate of incorporation of phenylalanine, decreased markedly with age. Fasting the rats for 20 hr did not change the principal age-related responsiveness of AIB transport to GH, but the magnitude of the hormone effect increased due to a lower uptake of AIB in control diaphragms. bGH had a dose-dependent effect on the accumulation of AIB in fasted 18-day old rats, the threshold concentration of bGH being 0.1 mug/ml. When diaphragms from 18-day old rats were incubated with bGH for various periods, the uptake of AIB was stimulated between 0 and 60 and 120 and 180 min, but not between 60 and 120 min after the start of the incubation. This observation indicated that the muscles were "refractory" to GH between 60 and 120 min. Preincubation of diaphragms from 21-day old rats with bGH for 3 hr did not inhibit the stimulatory effect of bGH added subsequently indicating that the duration of the "refractory phase" did not exceed 270 min in this group of rats. When diaphragms from fasted rats of different ages were preincubated in Krebs bicarbonate buffer for 3 hr, a stimulatory effect of bGH on AIB uptake was also observed in 26 and 30-day old rats, possibly because the influence of endogenous GH subsided during the preincubation period. These results suggest that diaphragms from "old" normal rats are insensitive to exogenous GH because the "refractory phases" become considerably prolonged with age.

Age Factors↗

Benn Index at birth is associated with postnatal linear growth.

While previous research has suggested that body thinness is related to subsequent linear growth in children, it is unclear whether thinness at birth is related to linear growth in newborns and catch-up growth in small-forgestational age newborns. Drawing on data from a longitudinal growth study of 3,650 full-term Swedish babies, this study examines linear growth from birth to 6 months of age in three groups of newborns with short (< -2 SDS), appropriate (-2 to 2 SDS) and long (> 2 SDS) body length for gestational age. Among infants short at birth, the Benn Index (kg/m2.69) at birth was not related to the odds of short stature (< -2 SDS) at age 6 months (odds ratio = 1.03; p > 0.10). Nonetheless, the Benn Index was positively related to growth velocity in the first 6 months of life in the short (p = 0.060), appropriate (p < 0.05), and tall (p < 0.05) for gestational age newborns. Use of the Ponderal Index (kg/m3) would give similar results. The findings suggest that nutritional status at birth is related to linear growth velocity in newborns.

Birth Weight↗