ROBUST GROWTH-HORMONE (GH) SECRETION IN AGED FEMALE RATS CO-ADMINISTERED GH-RELEASING HEXAPEPTIDE (GHRP-6) AND GH-RELEASING HORMONE (GHRH)

Aging is associated with a blunted growth hormone (GH) secretory response to GH-releasing hormone (GHRH), in vivo. The objective of the present study was to assess the effects of aging on the GH secretory response to GH-releasing hexapeptide (GHRP-6), a synthetic GH secretagogue. GHRP-6 (30-mu-g/kg) was administered alone or in combination with GHRH (2-mu-g/kg) to anesthetized female Fischer 344 rats, 3 or 19 months of age. The peptides were co-administered to determine the effect of aging upon the potentiating effect of GHRP-6 on GHRH activity. The increase in plasma GH as a function of time following administration of GHRP-6 was lower (p < 0.001) in old rats than in young rats; whereas the increase in plasma GH secretion as a function of time following co-administration of GHRP-6 and GHRH was higher (p < 0.001) in old rats than in young rats (mean Cmax = 8539 +/-790.6-mu-g/l vs. 2970 +/- 866-mu-g/l, respectively; p < 0.01) Since pituitary GH concentrations in old rats were lower than in young rats (257.0 +/- 59.8-mu-g/mg wet wt. vs. 639.7 +/- 149.2-mu-g/mg wet wt., respectively; p < 0.03), the results suggested that GH functional reserve in old female rats was not linked to pituitary GH concentration. The differential responses of old rats to individually administered and co-administered GHRP-6 are important because they demonstrate that robust and immediate GH secretion can occur in old rats that are appropriately stimulated. The data further suggest that the cellular processes subserving GH secretion are intact in old rats, and that age-related decrements in GH secretion result from inadequate stimulation, rather than to maladaptive changes in the mechanism of GH release.