Growth hormone/insulin-like growth factor-1 response to acute and chronic growth hormone-releasing peptide-2, growth hormone-releasing hormone 1-44NH(2) and in combination in older men and women with decreased growth hormonesecretion

To better appreciate the interactions of GHRF-2 and GHRH 1-44NH(2) on the r elease of GH in normal adult men and women with decreased GH secretion and low serum IGF-1 levels, a series of acute and chronic studies have been per formed (n = 5 men, 5 women). The acute iv bolus GH responses of these subje cts to the two peptides alone and together suggest that the decreased GH se cretion may be primarily due to a deficiency of the natural endogenous GHRP , ghrelin, rather than a decreased secretion of endogenous GHRH or excess s ecretion of SRIF. To determine whether the low GH response to GHRH was due to a limited capacity of pituitary to release GH, higher dosages of GHRP-2 alone were administered. At a dose of 1 mug/kg GHRP-2 the GH response was e ssentially the same as that elicited by 1 mug/kg GHRH + 0.1 mug/kg GHRP-2 w hile the GH response to 10 mug/kg GHRP-2 sc was about twice as high in both men and women. Although these subjects have a limited pituitary capacity t o release CH, which is also an indication of decreased CH secretion in the presence of low serum IGF-1 levels, this alone would not explain the low GH response to GHRH. Furthermore, the finding that a low dose of 0.1 mug/kg G HRP-2 augments the CH response to 1 mug/kg GHRH is strongly against an exce ss secretion of SRIF. Twenty-four hour profiles of GH secretion during plac ebo, GHRP-2, and various doses of GHRH alone and together with GHRP-2 were studied. In addition, 1 mug/kg/h GHRP-2 was infused continuously sc to thes e subjects for 30 d. The normal pulsatile secretion of CH as well as the se rum IGF-1 level was increased after 24 h and remained elevated for 30 d. Wi th a deficiency of endogenous GHRH, the GH response of GHRP-2 would be litt le to none, while in subjects with a deficiency of the natural GHRP, the GH response to GHRH would be more attenuated. Thus, in chronic deficiency the GH response would be expected to depend on the degree of the capacity of t he pituitary to release CH as well as the type(s) of hormonal deficiency.