Effectiveness of Growth Hormone (GH) Secretagogues in Diagnosing and Treating GH Secretory Deficiency in Aging Men

Summary: Growth hormone releasing peptide (GHRP) increases effect of growth hormone releasing hormone on inducing growth hormone release, even when not given immediately prior. GHRP probably blocks somatostatin. Levels of GHRP's natural equivalent probably drop during aging.

Interestingness: 1

Paper by Richard F Walker and Barry B Bercu in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.

(((Yet another growth hormone paper. This one at least is neatly done, sticking to only one specific issue and comes with an easy conclusion)))

(((In this study, the older group is a bunch of people between 37 and 68, the younger group is between 16 and 21. The results seem to only refer to the male subsets. These groups are tiny, with six people in some, and three in others)))

Old people release way less growth hormone (GH) than young people when given GH releasing hormone (GHRH), but they release about the same GH when given GH releasing peptide (GHRP) (((an artificial peptide found to release GH, not found yet in the body naturally))) in older as in younger people. The amount released due to GHRP is much higher than that produced when GHRH alone is given. The relative effect of GHRP is much higher in older people: young people released 1.5 times as much GH when given GHRP compared to GHRH, but older people released 20.5 times as much when given GHRP compared to GHRH. When given less GHRP, less GH is released (((this is part of what they want to show, making the connection that older people probably have lower levels of GHRP or equivalent))).

GHRP only enhances the effect of the present GHRH though. If GHRH receptors are blocked with antagonists, GHRP doses don't lead to increased GH release. Giving GHRH and GHRP combined also leads to greater release than the sum of the releases when given separately. This is consistent with GHRP acting as a functional blocker of somatostatin.

Giving older people GHRP for 10 days, and then giving them GHRH the day after, released much more GH than without the 10 days of preparation. Since GHRP is metabolysed in minutes, this means that GHRP is not just acting directly ((("GHRH signal transduction" is what the paper calls it))) (((the increases in these priming examples are much lower than the immediately-prior dosing though)))


Abstract follows:

This study was conducted primarily to determine the utility of recombinant growth hormone releasing hormone (GHRH) and xenobiotic GH-releasing peptide (GHRP) administered sequentially or in combination, as diagnostic agents for pituitary-based, GH secretory dysfunction in aging men. The secondary purpose was to test the hypothesis that loss of sensitivity to stimulation with GHRH during aging results, at least in part, from reduced exposure of the pituitary gland to the yet unknown, endogenous compound whose activity is stimulated by GHRP. Increases in serum GH following GHRH administration were significantly lower in older men than they were in adolescent and young adult men. In contrast, changes in serum GH following GHRP were comparable in the younger and older men. Because robust GH secretion in response to administration of exogenous GHRH or GHRP is interpreted as representing adequate concentrations of complementary endogenous GHRP and GHRH, respectively, the data suggested that older subjects were deficient in endogenous GHRP. Accordingly, it was of interest to determine whether priming with GHRP would restore the response to GHRH in these men. Ten consecutive days of priming with GHRP caused the responses to GHRH challenge to be significantly improved compared with responses observed before priming. GH secretion following co-administration of GHRH and GHRP were comparable in both age groups. The results of this study suggest that functional elements of pituitary somatotrophs directly related to expression of GHRH activity are intact during aging, but lose their effectiveness in part because of complementary secretagogue (endogenous GHRP analogy) deficiencies. Whereas priming with GHRP demonstrates the plasticity of GHRH signal transduction mechanisms in aging men, the data do not allow determination of whether GHRH or GHRP receptors or second messengers for either or both of these secretagogues become down-regulated. Future studies are designed to make these determinations and to further investigate and confirm the validaity of using GH scretagogues to reactivate the GH axis in the elderly.