In 8- and 20-month-old male rats, treated or not with growth hormone (GH) for 4 days, simultaneous evaluation of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SS) gene expression, GH secretion from anterior pituitaries (APs) in vitro (basal and GHRH-stimulated) and plasma IGF-I levels was performed. Twenty-month-old rats showed decreased GHRH mRNA levels, decreased GH secretion from APs in vitro (not responsive to GHRH stimulation) and reduced plasma IGF-I levels as compared to younger counterparts. SS mRNA levels were only slightly reduced in the hypothalamus of aged rats. Short-term administration of biosynthetic human GH (125 microgram/rat, twice daily, IP) to 8-month-old rats abolished the in vitro GHRH-stimulated GH release from APs and altered GH regulatory neuropeptides gene expression, i.e., reducing GHRH mRNA levels and increasing SS mRNA levels. In 20-month-old rats, hGH administration increased plasma IGF-I levels but did not change significantly GHRH and SS gene expression. These data indicate that the feedback effects exerted by circulating GH on GHRH and SS neurons, while evident in adult rats, are not detectable in aged rats.