Effect of C-terminal chain shortening on the insulin-antagonistic activity of human growth hormone 177–191

1982 ◽  
Vol 101 (1) ◽  
pp. 10-14 ◽  
Author(s):  
J. D. Wade ◽  
F. M. Ng ◽  
J. Bornstein ◽  
C. O. Pullin ◽  
J. S. Pearce
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Amino Acid ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Antagonistic Activity ◽  
Amino Acid Residues ◽  
Active Peptides ◽  
Terminal Chain

Abstract. Six synthetic C-terminal shortened fragments of the reduced and S-carbamidomethylated peptide corresponding to residues 177 to 191 of human growth hormone (Cam-hGH 177–191) were assayed for insulin antagonistic activity in vivo. Two of the peptides, CamhGH 177–191 and cam-hGH 177–191 were, in nanomolar quantities, both active in that they caused significant hyperglycaemia and insulin resistance in normal rats. The remaining peptides, hGH 177–180, Cam-hGH 177–185, Cam-hGH 177–187 and hGH 177–189 were all inactive even at up to one hundred times the dose employed for the active peptides. The results indicate that an insulin antagonistic core of hGH is contained within amino acid residues 178 to 190 inclusive.

Reduced and S-carboxymethylated human growth hormone: a probe for diabetogenic action

1984 ◽  
Vol 247 (5) ◽  
pp. E639-E644
Author(s):  
C. M. Cameron ◽  
J. L. Kostyo ◽  
J. A. Rillema ◽  
S. E. Gennick
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Mouse Mammary Gland ◽  
Amino Acid Incorporation ◽  
Acid Incorporation ◽  
Hypophysectomized Rats

The biological activity profile of reduced and S-carboxymethylated human growth hormone (RCM-hGH) was determined to establish its suitability for study of the diabetogenic property of hGH. RCM-hGH was found to have greatly attenuated in vivo growth-promoting activity in the 9-day weight-gain test in hypophysectomized rats (approximately 1%) and to have a similar low order of in vitro activity in stimulating amino acid incorporation into the protein of the isolated rat diaphragm. RCM-hGH also only had approximately 1% of the in vitro insulin-like activity of the native hormone on isolated adipose tissue from hypophysectomized rats. In contrast, RCM-hGH retained substantial in vivo diabetogenic activity in the ob/ob mouse, appearing to have approximately 50% of the activity of the native hormone. RCM-hGH was also found to retain significant, although attenuated (25%), in vitro lactogenic activity when tested for the ability to stimulate amino acid incorporation into a casein-rich protein fraction in mouse mammary gland explants. Because RCM-hGH exhibits a high degree of diabetogenic activity, although lacking significant anabolic or insulin-like activities, it will be useful as a "monovalent" probe for the study of the molecular mechanism of the diabetogenic action of GH.

scholarly journals 468 AMINO ACID RESIDUES 93–96 OF THE HUMAN GROWTH HORMONE MOLECULE ARE IMPORTANT FOR POLYCLONAL ANTISERUM RECOGNITION

1985 ◽  
Vol 19 (4) ◽  
pp. 188A-188A
Author(s):  
Wendy J Maury ◽  
Alan P Rogol ◽  
Thaddeus E Kelly ◽  
Christopher Y Thomas
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Polyclonal Antiserum ◽  
Amino Acid Residues

scholarly journals Tryptic digestion of peptides corresponding to modified fragments of human growth hormone-releasing hormone.

2004 ◽  
Vol 51 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Ewa Witkowska ◽  
Alicja Orłowska ◽  
Jan Izdebski
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Human Growth Hormone ◽  
Proteolytic Enzymes ◽  
Human Growth ◽  
Peptide Bond ◽  
Growth Hormone Releasing Hormone ◽  
Amino Acid Residues ◽  
Releasing Hormone ◽  
Hydrolysis Process

The objective of this study was to examine the degradation of short peptides corresponding to modified fragments of human growth hormone-releasing hormone by trypsin. Six analogues of pentapeptide 9-13 of human growth hormone-releasing hormone containing homoarginine, ornithine, glutamic acid, glycine, leucine or phenylalanine residue in position 11, two analogues of hexapeptide 8-13 of human growth hormone-releasing hormone and two analogues of heptapeptide 7-13 of human growth hormone-releasing hormone containing homoarginine or glycine residue in position 11 were obtained. The peptides were subjected to digestion by trypsin and the course of reaction was monitored using HPLC. It was found that the rate of hydrolysis of the Lys(12)-Val(13) peptide bond depends on the amino-acid residue preceding Lys(12). The extension of the peptide chain towards the N-terminus by introduction of consecutive amino-acid residues corresponding to the human growth hormone-releasing hormone sequence accelerates the hydrolysis process. These results may be of assistance in designing new analogues of human growth hormone-releasing hormone, more resistant to the activity of proteolytic enzymes.

Hyperglycemic action of synthetic C-terminal fragments of human growth hormone.

1978 ◽  
Vol 234 (5) ◽  
pp. E521
Author(s):  
F M Ng ◽  
J Bornstein
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Biologically Active ◽  
Active Peptides ◽  
Intravenous Insulin ◽  
Insulin Tolerance ◽  
In Vivo Effects

The synthetic peptides corresponding to amino acids 172-191, 176-191, 177-191, 178-191, 179-191, and 180-191 of human growth hormone (hGH) have been studied for their in vivo effects in normal rats. Four of the peptides (hGH 172-191, 176-191, 177-191, and 178-191) produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin, whereas the other two (hGH 179-191 and 180-191) were inert in the systems tested. A single dose (5 nmol/kg body wt) of the peptides containing the amino acids sequence 178-191 of the hGH molecule significantly reduced insulin sensitivity of the animals in intravenous insulin tolerance tests. The findings also indicate that the biologically active peptides must not only have the minimum of the informational sequence but also that this must be in correct physical configuration.

The minimal amino acid sequence of the insulin-potentiating fragments of human growth hormone: its mechanism of action

Diabetes ◽  
1980 ◽  
Vol 29 (10) ◽  
pp. 782-787 ◽  
Author(s):  
F. M. Ng ◽  
J. Bornstein ◽  
C. E. Pullin ◽  
J. O. Bromley ◽  
S. L. Macaulay
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Human Growth Hormone ◽  
Mechanism Of Action ◽  
Human Growth

Design and in vivo evaluation of solid-in-oil suspension for oral delivery of human growth hormone

2008 ◽  
Vol 41 (2) ◽  
pp. 106-110 ◽  
Author(s):  
Hiromu Yoshiura ◽  
Yoshiro Tahara ◽  
Masakazu Hashida ◽  
Noriho Kamiya ◽  
Akihiko Hirata ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Oral Delivery ◽  
Human Growth ◽  
In Vivo Evaluation

New Gaba-containing analogues of human Growth Hormone Releasing Hormene (1–30)-amide: II. Detailed in vivo biological examinations

1993 ◽  
Vol 16 (10) ◽  
pp. 799-805 ◽  
Author(s):  
Magdolna Kovàcs ◽  
I. Mezõ ◽  
I. Teplán ◽  
M. Hollósi ◽  
J. Kajtár ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth

Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system

2004 ◽  
Vol 100 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Verena M. Leitner ◽  
Davide Guggi ◽  
Alexander H. Krauland ◽  
Andreas Bernkop-Schnürch
Keyword(s):  
Growth Hormone ◽  
Delivery System ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Nasal Delivery ◽  
In Vivo Evaluation

scholarly journals Amino acid substitutions in human growth hormone affect coiled-coil content and receptor binding

2021 ◽  
Author(s):  
Andrei Rajkovic ◽  
Sandesh Kanchugal ◽  
Eldar Abdurakhmanov ◽  
Rebecca Howard ◽  
Astrid Gräslund ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Binding Site ◽  
Human Growth Hormone ◽  
Receptor Binding ◽  
Coiled Coil ◽  
Human Growth ◽  
Zinc Binding ◽  
Amino Acid Substitutions ◽  
Great Relevance

The interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has great relevance to human diseases such as acromegaly and cancer. HGH has been extensively engineered by other workers to improve binding and other properties. We used a computational screen to select substitutions at single hGH positions within the hGHR-binding site. We find that, while many successfully slow down dissociation of the hGH-hGHR complex once bound, they also slow down the association of hGH to hGHR. We are particularly interested in E174 which belongs to the hGH zinc-binding triad, and which spans coiled-coil helices and obeys the coiled-coil heptad pattern. Surprisingly, substituting E174 with A leads to substantial increase in an experimental measure of coiled-coil content. E174A is known to increase affinity of hGH against hGHR; here we show that this is simply because the off-rate is slowed down more than the on-rate, in line with what has been found for other affinity-improving mutations. For E174Y (and mutations at other sites) the slowdown in on-rate was greater, leading to decreased affinity. The results point to a link between coiled-coiling, zinc binding, and hGHR-binding affinity in hGH, and also suggest rules for choosing affinity-increasing substitutions.

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