This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The unnatural pentapeptide GHRPs appeared in 1976. GHRP-GHRH was found to synergistically release GH in rats in 1984, indicating the peptides' complementary and independent actions. GHRP was hypothesized to reflect the activity of a new hypothalmic hormone. By 1989, the GHRP GH release in humans was notable, and, by 1996, the GHRP-GHS receptor was cloned. The natural hormone, grehlin, has been isolated by Kojima et al. The chemistry and the major anatomical site of origin are novel since it is a Ser3-octanolyated 28 amino acid peptide that appears to originate in the stomach but also is present in the ventral lateral border of the hypothalamic acuate nucleus. Our preliminary results in rats support that natural ghrelin has the same GH releasing activity as the biological actions of unnatural GHRP. In vitro and in vivo studies in rats, dogs, and humans have been proposed to pursue the hypothesis that 1) ghrelin is the physiological endogenous GHRP hormone, 2) GHRP-2 and ghrelin essentially have the same biological actions, and 3) natural GHRP, ghrelin, deficiency is responsible for the decreased GH secretion of some normal older humans. We now have methods to measure the basal levels of ghrelin. We have used commercial RIA kits and are attempting to establishan RIA in our laboratory to determine ghrelin levels in plasma/serum. This will enable us to ascertain the levels of circulating ghrelin of different individuals at various times of the day, before and after meals, in order to assess the precision and differences in the levels of this peptide between subjects.
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