Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of prostaglandins on the incorporation of [4,5-(3)H]leucine into growth hormone and its subsequent release into the incubation medium were studied. Incubation of rat anterior pituitary glands with 10(-6) M prostaglandin PGE(1) in tissue culture medium 199 for 7 hr caused a 40-300% increase in the release of labeled growth hormone into the incubation medium. PGE(1) at 10(-8) M increased growth hormone synthesis but not release. At 10(-6) M, PGE(2) had effects similar to PGE(1); PGA(1) increased growth hormone synthesis but not release. PGF(2alpha) was without effect on either synthesis or release of growth hormone.Prolactin synthesis and release were not affected by prostaglandins. All of the prostaglandins, at 10(-4) M, increased adenyl cyclase activity in the pituitary gland but phosphodiesterase activity was unaltered. Dibutyryl cyclic AMP, with or without caffeine, caused an up to 300% increase in labeled growth hormone release. No consistent effect of prolactin was observed. If potassium concentration was increased 10-fold, a 215% increase in growth hormone release was observed. A combination of hypertonic potassium and 10(-6) M PGE(1) increased growth hormone release 325%, suggesting that potassium and prostaglandins act by independent mechanisms. Addition of theophylline to pituitary gland, incubated in vitro, increased both the synthesis and release of growth hormone. Although fluoride greatly stimulated growth hormone release, it completely inhibited the incorporation of leucine into the hormone. Similarly, puromycin inhibited synthesis of growth hormone but did not block release induced by prostaglandin, dibutyryl cyclic AMP, theophylline, or fluoride. Prostaglandins increase pituitary adenyl cyclase activity and, presumably via cyclic AMP, increase growth hormone release, independently of protein synthesis.
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PMID:Release of pituitary growth hormone by prostaglandins and dibutyryl adenosine cyclic 3':5'-monophosphate in the absence of protein synthesis. 432 Sep 73

The gastric acid and pepsin inhibitory activities of 21 analogues of somatostatin, the majority modified at position 8, were determined in conscious cats in order to examine the importance of Trp8 for the activity of somatostatin. Pepsin secretion stimulated by pentagastrin was 5 times more sensitive, compared with the acid secretion, to inhibition by somatostatin. All the analogues showed similar differential sensitivity, indicating a similar specificity of somatostatin receptors involved in the inhibition of these two secretions. Halogenated-Trp8 analogues of somatostatin were only equipotent or slightly more active than somatostatin against gastric secretion in the cat, whilst these analogues are up to 30 times more potent against growth hormone release in the rat, indicating a different specificity of the two groups of receptors. Studies with the position 8 modified analogues suggest that the electron density of the aromatic nucleus of Trp8 may be relatively unimportant in determining the gastric inhibitory activity, whilst it can be concluded that the role of Trp8 in somatostatin depends to a large extent on the indole NH group. The precise role of Trp8 in somatostatin could be an involvement in the binding of somatostatin to its receptors, or involvement in forming the biologically active conformation of somatostatin.
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PMID:Structure-activity studies with somatostatin: the role of tryptophan in position 8. 611 15

The limited proteolysis approach was used to analyze the conformational features of human growth hormone (hGH) under acidic solvent conditions (A-state). Pepsin was used as the proteolytic probe because of its poor substrate specificity and its activity at low pH. Limited proteolysis of hGH in its A-state results in a selective cleavage of the Phe44-Leu45 peptide bond, leading to the production of fragments 1-44 and 45-191. The two fragments were isolated in homogeneous form for studying their conformational properties by means of spectroscopic methods. Fragment 1-44 was shown to retain little secondary and tertiary structure at neutral pH, while fragment 45-191 independently folds into a highly helical secondary structure. In particular, we have shown that the two peptic fragments are able to associate into a stable and native-like hGH complex 1-44/45-191. Our proteolysis data indicate that in acid solution hGH adopts a partly folded state characterized by a local unfolding of the first minihelix (residues 38-47) encompassing the Phe44-Leu45 peptide bond. Of interest, hGH has both insulin-like and diabetogenic effects. Two fragments of hGH occur in vivo and exert these two opposite activities, namely, fragment 1-43 showing an insulin-potentiating effect and fragment 44-191 showing a diabetogenic activity. The results of this study suggest that the conformational changes of hGH induced by an acidic pH promote the generation of the two physiologically relevant fragments by proteolytic processing of the hormone. Although pepsin cannot be the enzyme responsible for the in vivo processing of the hormone, we propose that limited proteolysis of hGH at low pH is physiologically relevant, since the hormone is exposed to an acidic environment in the cell. This study reports for the first time the analysis of the conformational features of the two individual functional domains of hGH and of their complex.
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PMID:Limited proteolysis of human growth hormone at low pH: isolation, characterization, and complementation of the two biologically relevant fragments 1-44 and 45-191. 1515 90

The diffusion and mechanical properties of calcium alginate gels were determined using constructs of different alginate concentrations and guluronic acid contents. It was found that the diffusion of small molecules such as sulphate, glucose and thymidine was not impeded by any of the alginates tested at concentrations of 1% and 3% (w/v). By contrast, the diffusion of large molecules, including insulin like growth factor-1 (IGF-1), human growth hormone and bovine serum albumin was impeded by alginate. This effect was enhanced with increasing alginate concentration, but was less evident for alginates with increased guluronic acid content. These findings have significant implications in tissue engineering where cells such as chondrocytes depend on the supply of factors such as IGF-1 to remain viable. An increase in both alginate concentration and guluronic acid content also increased the compressive properties, as determined by both tangent and equilibrium modulus, of alginate constructs. Although the 3% alginate constructs exhibited enhanced stiffness compared to some reported cartilage substitute biomaterials, such as PGA, their absolute values were still appreciably less stiff than articular cartilage.
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PMID:Concentration and M/G ratio influence the physiochemical and mechanical properties of alginate constructs for tissue engineering. 2079 7