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

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.