Age-related variations in the growth hormone response to growth hormone secretagogues

Growth hormone (GH) secretagogues are synthetic peptidyl and non-peptidyl molecules which possess a strong, dose-dependent and reproducible GH-releasing effect after intravenous and even oral administration in humans. This effect is probably mediated via the activation of specific receptors, mainly present at the pituitary and hypothalamic level; a human pituitary GH secretogogue receptor has already been cloned, pointing to the existence of an endogenous GH secretagogue-like ligand. The GH-releasing effect of GH secretagogues is gender-independent but undergoes marked age-related variations. In fact, the effect is low at birth, increases markedly at puberty, persists at a similar level in adulthood and decreases thereafter, being already similar in middle age to that in elderly subjects. It is likely that the reduced activity of GH secretagogues in aging reflects the age-related changes in the neural control of somatotrope function. These could include the hypothetical impairment in the activity of the p..

Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT

Ghrelin is an acyl-peptide gastric hormone acting on the pituitary and hypothalamus to stimulate growth hormone (GH) release, adiposity, and appetite. Ghrelin endocrine activities are entirely dependent on its acylation and are mediated by GH secretagogue (GHS) receptor (GHSR)-1a, a G protein–coupled receptor mostly expressed in the pituitary and hypothalamus, previously identified as the receptor for a group of synthetic molecules featuring GH secretagogue (GHS) activity. Des-acyl ghrelin, which is far more abundant than ghrelin, does not bind GHSR-1a, is devoid of any endocrine activity, and its function is currently unknown. Ghrelin, which is expressed in heart, albeit at a much lower level than in the stomach, also exerts a cardio protective effect through an unknown mechanism, independent of GH release. Here we show that both ghrelin and des-acyl ghrelin inhibit apoptosis of primary adult and H9c2 cardiomyocytes and endothelial cells in vitro through activation of extracellular signal–regulated kinase-1/2 and Akt serine kinases. In addition, ghrelin and des-acyl ghrelin recognize common high affinity binding sites on H9c2 cardiomyocytes, which do not express GHSR-1a. Finally, both MK-0677 and hexarelin, a nonpeptidyl and a peptidyl synthetic GHS, respectively, recognize the common ghrelin and des-acyl ghrelin binding sites, inhibit cell death, and activate MAPK and Akt

Biologically active drug polymer derivatives and method for preparing same

New biologically active drug polymer derivatives, namely peptides or protein derivatives, are useful medicaments and are represented by the generic formula: wherein R represents a lower alkyl group, n is an integer comprised between 25 and 250, X when combined with adjacent NH and CO groups represents an amino acid or a dipeptide or tripeptide residue, and Z when combined with the adjacent NH group represents a biologically active peptide or protein or NH or NH.sub.2 containing drug residue

growth hormone secretagogues: past, present and future

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