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S Eden

Publications and source records attributed to S Eden.

22 records · Page 2Linked to original sources

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↗

A hybrid noncovalent complex of fragments of porcine and human growth hormones with diabetogenic activity.

Although porcine GH (pGH) and human GH (hGH) are structurally related, their structures differ to the extent that, unlike hGH, pGH is not active in primates and does not exhibit lactogenic activity. Therefore, it was of interest to determine whether hybrid noncovalent complexes could be formed by complementation of large fragments of pGH with fragments of hGH and to study the immunological and biological properties of such hybrids. For this purpose, pGH was digested with bovine thrombin conjugated to Sepharose. After reduction and S-carbamidomethylation of the digested hormone, two large fragments consisting of residues 1-133 (p1-133T) and 134-191 (p134-191T) were isolated by gel filtration. The human GH fragments used in this work were S-carbamidomethylated peptides 1-134 (h1-134T) and 135-191 (h135-191T) isolated from thrombin-digested hGH. Noncovalent complementation of the peptide fragments was attempted by dissolving equimolar amounts of the materials in 0.5% (wt/vol) ammonium bicarbonate solution containing 6 M guanidine-HCl and then gradually removing the guanidine-HCl by dialysis. Using this method, a hybrid noncovalent complex of peptides p1-133T and h135-191T was produced in 50% yield by weight of starting material. Attempts to produce the reciprocal complex between h1-134T and p134-191T, as well as attempts to recombine the contiguous pGH fragments, p1-133T, and p134-191T, were unsuccessful. The hybrid complex (p1-133T + h135-191T) had 40% the cross-reactivity of native pGH in a rat GH RIA, but it was inert in an hGH RIA. It had very low growth-promoting activity in the 9-day weight gain test in hypophysectomized rats and no detectable in vitro ability to stimulate [14C]phenylalanine incorporation into the protein of the diaphragm of the hypophysectomized rat. When tested for insulin-like activity (stimulation of glucose oxidation in vitro in adipose tissue of hypophysectomized rats), the hybrid complex had less than 1% the activity of native pGH. In contrast, the hybrid complex had approximately 10-20% the diabetogenic activity of native pGH in the ob/ob mouse. The fact that the hybrid complex has substantial diabetogenic activity, although lacking significant anabolic or insulin-like activities, suggests that the structural requirements differ for the expression of these various activities of GH.

Adipose Tissue↗

Evidence for a growth hormone releasing factor mediating alpha-adrenergic influence on growth hormone secretion in the rat.

The effects of adrenergic receptor agonists on GH secretion were studied in adult, male rats pretreated with reserpine and somatostatin antiserum. Frequent blood samples were obtained from intra-aortic cannulae. Plasma GH was determined by radioimmunoassay. Reserpine (10 mg/kg i.p.) caused a complete suppression of the normal, pulsatile secretion of GH in all animals. Administration of somatostatin antiserum resulted in rapid elevations of plasma GH in reserpine-pretreated rats with peak levels at 30 min. GH levels then fell but remained slightly elevated for the duration of the sampling period (8 h). Apomorphine (0.5 mg/kg i.p.) had no effect on plasma GH levels, whereas clonidine (0.5 mg/kg i.p.) induced release of GH in both antiserum treated and control rats. The results indicate that the alpha-adrenergic influence on the secretion of GH is mediated not by inhibition of somatostatin release but rather by effects on the release of a GHRF.

Animals↗

Effect of LH on the release of cyclic AMP by the rabbit ovary perfused in vivo and in vitro.

After perfusion of 10 rabbit ovaries in vitro with a modified Krebs bicarbonate buffer containing dextran and glucose, the concentration of cAMP in the perfusion medium was significantly increased 2-5 min after stimulation with 10 mug LH/ml medium and was higher at 15 and 30 min. Intravenous injection of 100 mug LH/rabbit caused a significant increase of cAMP concentrations in the ovarian venous blood from 8 ovaries 10 min after the injection and the cAMP concentrations were higher after 15 and 30 min. The ovarian blood flow was not changed after the LH injection. It is concluded that perfusion techniques can be useful in analysis of the mechanisms and physiological significance of release of cAMP from the ovary after hormonal stimulation.

Animals↗