An enzymatic model of the growth hormone-releasing hormone oscillator incorporating neuronal synchronization.

Models of growth hormone (GH) rhythmogenesis which we and others have presented suggest that the GH pulses in the circulation are generated by a GH-releasing hormone (GHRH) oscillator with a 1h periodicity. Here we examine the possibility that this is an intrinsic neuronal rhythm resulting from enzymatic reactions occurring in the axon terminals. A "Baselator" feedback reaction sequence can generate an hourly chemical burst of a primer (presumably a low molecular weight peptide) regulating Ca(2+)-triggered exocytosis of GHRH-loaded vesicles.

Elevated circulating acylated and total ghrelin concentrations along with reduced appetite scores in infants with failure to thrive.

Failure to thrive (FTT) is a term used to describe inadequate growth in infants. The immediate cause is undernutrition. Ghrelin is a potent orexigenic hormone that induces a positive energy balance and enhances appetite.

Subcellular dynamics of somatostatin receptor subtype 1 in the rat arcuate nucleus: receptor localization and synaptic connectivity vary in parallel with the ultradian rhythm of growth hormone secretion.

Growth hormone (GH) secretion in male rats exhibits a 3.3 h ultradian rhythm generated by the reciprocal interaction of GH-releasing hormone (GHRH) and somatostatin (SRIF). SRIF receptor subtypes sst(1) and sst(2) are highly expressed in GHRH neurons of the hypothalamic arcuate nucleus (ARC).

Interactions of ghrelin signaling pathways with the GH neuroendocrine axis: a new and experimentally tested model.

Growth hormone (GH) is secreted in a pulsatile fashion from the pituitary gland into the circulation. Release is governed by two hypothalamic neuropeptides, growth hormone-releasing hormone (GHRH) and somatostatin (SRIF), resulting in secretion episodes with a periodicity of 3.3 h in the male rat.

Pharmacological demarcation of the growth hormone, gut motility and feeding effects of ghrelin using a novel ghrelin receptor agonist.

The peptide hormone ghrelin exerts a wide spectrum of activities including the stimulation of GH release, feeding, and gastrointestinal motility, purportedly via the activation of a common receptor, GH secretagogue receptor (since renamed the GRLN-R) The aim of the present study was to determine whether these effects can be separated pharmacologically. Tranzyme Pharma (TZP)-101 is a small-molecule agonist with potent binding affinity (inhibitory constant = 16 nm) and full agonist activity (EC50 = 29 nm, maximum response = 111%) at the human recombinant GRLN-R. Pharmacokinetic profiling of TZP-101 in rat determined a plasma elimination half-life of 99 min and low blood-brain barrier permeability (0.