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Biomedical subjects

O Isaksson

Publications and source records attributed to O Isaksson.

At least 55 records · Page 3Linked to original sources
PubMed1984

The antilipolytic, insulin-like effect of growth hormone is caused by a net decrease of hormone-sensitive lipase phosphorylation.

The mechanism of the antilipolytic effect of GH and the cause of refractoriness to its own action was studied in isolated rat adipocytes. Human GH rapidly inhibited catecholamine-stimulated lipolysis rate, with a time course similar to that of insulin, but only in cells which had been preincubated in the absence of GH for 2-3 h. Half-maximal inhibition was obtained with a GH concentration of 100 ng/ml. Parallel determinations of the lipolysis rate (with a pH-stat titration technique) and the extent of phosphorylation of hormone-sensitive lipase, the rate-controlling enzyme in adipose tissue lipolysis, were made. The extent of lipase phosphorylation, 1.7-fold enhanced by previous noradrenaline stimulation, was rapidly reversed by addition of GH, and the decrease was followed by a parallel decrease in the lipolysis rate. The time course and magnitude of these effects was similar to those obtained with exposure of the cells to insulin, indicating that the antilipolytic effect of both hormones was exerted through the same mechanism: a net dephosphorylation of the hormone-sensitive lipase. To study the refractoriness of the fat cells to the action of GH (which was not found with insulin) adipocytes were prepared from hypophysectomized rats 24 h after surgery. With such cells no preincubation was required to obtain the effects of GH on the lipolysis rate and extent of hormone-sensitive lipase phosphorylation. The effects of GH on both of the parameters studied were similar to those obtained in nonhypophysectomized rats. These results suggest that the refractoriness of the fat cells to GH may be explained by a functional inhibition at a site(s) in the series of metabolic events initiated by GH action, which precedes the activation of the hormone-sensitive lipase.

Adipose Tissue↗
PubMed1983

Rat growth hormone and hypothalamic catecholamine nerve terminal systems. Evidence for rapid and discrete reductions in dopamine and noradrenaline levels and turnover in the median eminence of the hypophysectomized male rat.

Rat growth hormone (rGH) (100 micrograms/kg) produced 2-4 h after its i.v. injection a rapid reduction of catecholamine stores and turnover in the subependymal layer and in the medial and lateral palisade zone of the median eminence. It is suggested that rGH may inhibit its own secretion partly via reduction of DA synthesis and release in the median eminence leading to increased somatostatin release and partly via reduced noradrenaline synthesis and turnover in the median eminence leading to reduced secretion of a growth hormone releasing factor.

Animals↗
PubMed1983

Regulation of sexually dimorphic hepatic steroid metabolism by the somatostatin-growth hormone axis.

Lesions in the periventricular hypothalamic area in male rats results in a "feminization" of steroid metabolizing enzymes in the liver. These lesions also resulted in a decrease of somatostatin levels in the median eminence. Since blockade of somatostatin by in vivo administration of an antiserum also caused "feminization" of the liver, it is possible that at least one hypothalmic factor responsible for "feminization" is related to somatostatin. Also extrahypothalmic areas seem to influence sexually differentiated functions in the liver. The neuroendocrine control of the "feminizing factor" secretion from the pituitary bears several resemblances to the central control of GH. The hypothesis that the plasma pattern of GH regulates hepatic steroid metabolism in the rat was studied in two different animal models: (1) Different plasma patterns of GH were achieved by administration of human GH (hGH) at different frequencies or by infusing the hormone continuously by means of Alzet osmotic minipumps to hypophysectomized female rats. (2) The plasma pattern of GH in animals with an intact pituitary gland was investigated under conditions which lead to "feminization" of hepatic steroid metabolism. The results demonstrate that the plasma pattern of GH influences hepatic steroid metabolism. Increased trough plasma GH values or absence of time periods with undetectable plasma levels of GH appears to be a major determinant for "feminization" of hepatic steroid metabolism. Since sex steroids were found to influence the plasma pattern of GH it seems as if differences in the plasma pattern of GH between male and female rats explain the sex-differentiated hepatic steroid metabolism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1983

Sites of action of testosterone and estradiol on longitudinal bone growth.

In this study the mechanisms by which sex steroids influence body growth were investigated. The effect of different doses of testosterone propionate on longitudinal bone growth and body weight gain was studied in a) gonadectomized male rats, b) gonadohypophysectomized male rats, and c) gonadohypophysectomized male rats given replacement therapy with bovine growth hormone (bGH). The effect of different doses of estradiol benzoate on the same growth parameters was studied in female rats divided into the same experimental groups as the males. Accumulated longitudinal bone growth was determined using oxytetracycline as an intravital marker. Testosterone caused a dose-dependent increase in longitudinal bone growth in gonadectomized male rats. In contrast, testosterone exerted no significant increase in longitudinal bone growth in gonadohypophysectomized male rats with and without bGH replacement therapy. Treatment with estrogen inhibited longitudinal bone growth and body weight gain. The inhibitory effect of estradiol was approximately the same in gonadohypophysectomized female rats given bGH replacement therapy as in gonadectomized female rats. The results suggest that testosterone exerts its stimulatory effect on body growth mainly by modulating hypothalamopituitary functions, e.g., by altering the secretory pattern of GH. On the other hand, it seems that changes in the hypothalamopituitary functions are less significant for the inhibitory effect of estradiol on body growth. It is concluded from this study that the sites of action for estrogen and testosterone in modulating body growth in the rat are different.

Aging↗
PubMed1983

Effects of in vivo administration of antiserum to rat growth hormone on body growth and insulin responsiveness in adipose tissue.

To explore the short term effects of endogenous GH on body growth, glucose metabolism, and insulin responsiveness in adipose tissue, 35- to 40-day-old male rats were treated with a potent goat antiserum against rat GH (ArGHS). The administration of ArGHS, but not normal goat serum, caused a dose-dependent decrease in body weight gain and longitudinal bone growth, as measured by the tetracycline method. Glucose metabolism was measured by determining the production of CO2 from [14C]glucose in epididymal fat pad. Treatment with ArGHS (0.05-0.5 ml, ip, twice daily for 6 days) resulted in increased insulin sensitivity, as determined by the ED50 values for the effect of insulin. An increased response to a submaximal concentration of insulin was observed 3 h after the administration of 0.5 ml ArGHS. Basal levels were not consistently affected by ArGHS treatment. The maximal response to insulin was significantly increased after treatment with low doses of ArGHS (0.1-0.2 ml/day) and was decreased after treatment with high doses of ArGHS (0.8-1 ml/day) for 6 days. The magnitude of the response, as determined by the percent increase in response to 10 mU/ml insulin, was, however, not different compared to that observed in adipose tissue of normal goat serum-treated rats. These results demonstrate that elimination of endogenous GH results in retarded growth in the rat within 24 h. Moreover, the results suggest that GH is important in insulin sensitivity.

Adipose Tissue↗
PubMed1983

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↗
PubMed1982

Isolation of rat pituitary prolactin isohormones differing in charge, size, and specific immunological activity.

A method has been described for the isolation of three differently charged isohormones of rat prolactin from a discard fraction obtained after extraction of gonadotropins, thyrotropin and growth hormone from homogenized frozen pituitaries. The procedure involved extraction at pH 9.8, ammonium sulphate fractionation, molecular sieve chromatography on Sephadex G-100, and column electrophoresis in agarose suspension. The purification was monitored by radioimmunoassays and the recovered components were all found to possess a specific immunoactivity exceeding that of the standard preparation (RP-1) supplied by the NIAMDD, Bethesda, U.S.A. Increased acidity among these isohormones was found to be paralleled by significantly decreased immunopotency. Each component showed biological activity in radioreceptor assay. A high degree of purity of the isolated components was shown by analytical electrophoresis in polyacrylamide gel. Sodium dodecyl sulphate electrophoresis in the same medium showed no size heterogeneity and yielded a value of approximately 25 000 for the molecular weight of the isohormones. In addition a large form of prolactin, suggested to represent a dimer, was isolated by a further extraction step (pH 10.5) followed by molecular sieve chromatography on Sephadex G-100 and electrophoresis in agarose suspension. The large form was associated with both biopotency and immunopotency. The electrophoresis resolved the prolactin activity into three or four immunoactive components. This pleomorphism of the large prolactin was confirmed by analytical polyacrylamide gel electrophoresis. Amino acid analyses revealed a close similarity between the three monomers and the major dimeric form of the hormone.

Amino Acids↗
PubMed1982

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↗
PubMed1982

Ovulation induced by a gonadotropin releasing hormone analog in hypophysectomized rats involves prostaglandins.

A potent analogue of gonadotropin releasing hormone [D-Ala6- Des-Gly10-NH2]-GnRH ethylamide (GnRHa) caused oocyte maturation and ovulation when injected in the afternoon of proestrus in immature PMSG-treated female rats, hypophysectomized on the morning of proestrus. This action of GnRHa was accompanied by a marked increase in ovarian PGE levels. Furthermore, the pretreatment of the animals with a prostaglandin synthetase inhibitor (indomethacin) completely inhibited this PGE increase and ovulation. These data suggest a role for prostaglandins in GnRHa induced ovulation.

Animals↗
PubMed1982

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↗
PubMed1981

Gonadotropin releasing hormone agonists stimulate oocyte meiosis and ovulation in hypophysectomized rats.

The acute effects in vivo of gonadotropin releasing hormone (GnRH) and a potent agonistic analogue (GnRHa) were tested in PMSG-treated immature female rats, hypophysectomized on the morning of proestrus. The rats were injected once with either LH, GnRH, or GnRHa 3-4 h after surgery, and the effects on oocyte meiosis, ovulation, and plasma progesterone were investigated. LH (25 microgram) and GnRHa (12.0 and 1.2 microgram) caused a high rate of meiosis, while GnRH (100 microgram) or GnRHa (0.12 microgram) caused a partial response. LH and GnRHa produced ovulation in all of the treated rats and caused a prolonged increase in plasma progesterone levels. It is concluded that GnRH agonists exert acute stimulatory effects in the ovarian follicle, independent of pituitary factors.

Animals↗
PubMed1980

Sustained cardiac beta adrenoceptor blockade in vitro and increased vulnerability to aconitine-induced arrhythmias in vivo after propranolol withdrawal in rats.

The present study was undertaken in order to investigate the possibility of cardiac hypersensitivity to norepinephrine (NE) after propranolol withdrawal in rats. The effect of NE was studied on heart rate and left intraventricular pressure development (maximal dP/dt) in the isolated perfused heart at various time periods after termination of the propranolol feeding. Also, the influence of propranolol withdrawal on vulnerability to aconitine-induced arrhythmias in vivo was evaluated in anesthetized rats. No hypersensitivity to NE was seen in the perfused rat heart 1 and 3 days after propranolol withdrawal. Rather, a depressed response to NE was registered suggesting a long half-life for the disappearance of beta adrenoceptor blockade. Increased vulnerability to aconitine-induced arrhythmias was observed 1 and 3 days after treatment with propranolol had ceased. Rats receiving propranolol continuously until experimentation exhibited an elevated threshold to aconitine-induced arrhythmias. These data indicate that a hypothetical rebound phenomenon after withdrawal of propranolol is not associated with an increase in mechanical performance of the heart in response to NE. A decreased threshold for development of arrhythmias appears, however, to be at hand, perhaps due to an inbalance in the transmembrane sodium flux in the heart in the early time course after propranolol withdrawal.

Aconitine↗
PubMed1979

In vitro effects of growth hormone on protein synthesis and amino acid transport in the rat diaphragm after acute hypophysectomy.

The effects of growth hormone (GH) in vitro on phenylalanine-14C incorporation to assess protein synthesis and on alpha-aminoisobutyric-1-3H accumulation to measure amino acid transport in the diaphragm muscle of the rat were investigated 2, 6 and 24 h after hypophysectomy or sham-operation. In hypophysectomized animals protein synthesis was depressed. GH in vitro was without effect 2 h after hypophysectomy but stimulated protein synthesis 6 and 24 h after the operation. Six hours after hypophysectomy amino acid transport was enhanced and further stimulated by GH. After 24 h amino acid transport was depressed but was stimulated to normal levels by GH. Six hours after sham-operation protein synthesis was depressed, but was stimulated by GH. After 24 h protein synthesis was normalized and GH was without effect. GH did not influence amino acid transport after sham-operation. Plasma levels of GH were undetectable after hypophysectomy, markedly depressed 2 and 6 h after sham-operation, but normal after 24 h. It is concluded that tissue responsiveness to GH develops a few hours after hypophysectomy.

Amino Acids↗