Inhibition of GH Release in Rats by New Potent Antagonists of Growth Hormone-Releasing Hormone (GH-RH)

  title={Inhibition of GH Release in Rats by New Potent Antagonists of Growth Hormone-Releasing Hormone (GH-RH)},
  author={Magdolna Kov{\'a}cs and Andrew V. Schally and M{\'a}rta Zar{\'a}ndi and Kate Groot},
Synthesis and biological evaluation of antagonists of growth hormone-releasing hormone with high and protracted in vivo activities.
High and protracted in vivo activities of these hGH-RH antagonists indicate an improvement over earlier GH-RH analogs, and could find clinical applications in the treatment of cancers dependent on insulin-like growth factors I and II.
New analogs of human growth hormone-releasing hormone (1-29) with high and prolonged antagonistic activity.
  • K. Tóth, M. Kovács, A. Schally
  • Chemistry, Biology
    The journal of peptide research : official journal of the American Peptide Society
  • 1998
All the analogs were evaluated for their ability to inhibit GH release induced by hGHRH(1-29)NH2 in vitro and some were also tested in vivo and showed high and prolonged inhibitory effect in superfused rat pituitary system.
Effects of antagonists of growth hormone-releasing hormone (GHRH) on GH and insulin-like growth factor I levels in transgenic mice overexpressing the human GHRH gene, an animal model of acromegaly.
It is suggested that this class of analogs could be used for the diagnosis and therapy of disorders characterized by excessive GHRH secretion, and the suppression of circulating GH concentrations induced by the antagonists seems to be physiologically relevant.
Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers
It is demonstrated that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro, and may be mediated through a reduced production and secretion of IGF-II by cancer cells.
Inhibitory Effects of GHRH Antagonists on Human GH-Secreting Adenoma Tissue
This study provides direct evidence for the effectiveness of potent GHRH antagonists such as MZ-4-71 and JV-1-36 on human pituitary GH-secreting adenoma tissue and strongly suggests that these drugs could be used for therapy of G HRH-associated forms of acromegaly, particularly for those patients in whom surgery fails or is not an option.
Inhibitory effects of antagonistic analogs of GHRH on GH3 pituitary cells overexpressing the human GHRH receptor.
It is demonstrated that G HRH antagonists can effectively inhibit the actions of GHRH on the hGHRH-R, and the view that this class of compounds would be active clinically is supported.


Synthesis and biological activities of highly potent antagonists of growth hormone-releasing hormone.
In the search for antagonists of human growth hormone-releasing hormone (hGHRH) with high activity, 22 analogs were synthesized by solid-phase methods, purified, and tested biologically and found to have high affinities to rat pituitary GHRH receptors.
Synthetic analogs of growth hormone-releasing factor with antagonistic activity in vitro.
Effects of acute and chronic administration of a new potent antagonist of growth hormone-releasing hormone in rats: mechanisms of action.
GHRH antagonist MZ-4-71 is effective in vivo and that it can inhibit growth and secretion of GH and IGF-I in rats and provides new information on the role of GHRH in regulating synthesis ofGH and G HRH receptors.
Suppression of growth hormone (GH) secretion by a selective GH-releasing hormone (GHRH) antagonist. Direct evidence for involvement of endogenous GHRH in the generation of GH pulses.
These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans.
A method for evaluation of activity of antagonistic analogs of growth hormone-releasing hormone in a superfusion system.
  • Z. Rékási, A. Schally
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
This sensitive dynamic in vitro system appears to be a suitable method for screening the biological activity of various GHRH antagonists and eliminates the drawbacks of static pituitary cell culture.
Structural requirements for the activation of rat anterior pituitary adenylate cyclase by growth hormone-releasing factor (GRF): discovery of (N-Ac-Tyr1, D-Arg2)-GRF(1-29)-NH2 as a GRF antagonist on membranes.
It was possible to demonstrate that GRF and vasoactive intestinal peptide receptors represent distinct entities in the rat anterior pituitary.
Analogues of growth hormone-releasing factor (1-29) amide containing the reduced peptide bond isostere in the N-terminal region.
The analogue [Ser9 psi[CH2NH]Tyr10]GRF(1-29)NH2 was found to be an antagonist in the 10 microM range vs 1 nM GRF and had no agonist activity at doses as high as 0.1 mM.