INADEQUATE PITUITARY STIMULATION - A POSSIBLE CAUSE OF GROWTH-HORMONEINSUFFICIENCY AND HYPERPROLACTINEMIA IN AGED RATS

Although old animals respond poorly to exogenous growth hormone releas ing hormone (GHRH), acute coadministration of GHRH and GH releasing he xapeptide (GHRP) stimulated more GH release in old rats than in young rats (Walker et al., 1991). The purpose of the present study was to ev aluate the effects of chronically co-administered GH secretagogues in old rats. The initial GH hypersecretory response in 22 month old rats abated rapidly to normal youthful values, so that by 5 days of treatme nt GH secretory patterns were quantitatively and temporally indistingu ishable from those in young rats. Co-administration of GHRH and GHRP t o the old rats for 120 consecutive days also increased pituitary GH an d serum IGF-1 concentrations indicating that the secretagogues stimula ted synthesis as well as release of bioactive GH. Furthermore, pituita ry weight, macroadenomas and hyperprolactinemia decreased, while pitui tary prolactin (PRL) concentrations increased in old rats treated with the GH secretagogues. The increased concentrations of pituitary GH an d PRL were accompanied by increased concentrations of GH mRNA and PRL mRNA indicating that the molecular processes for synthesis of the two hormones were stimulated by GH secretagogue administration. These data suggest that reduced activity of the GH neuroendocrine axis during ag ing results at least in part, from inadequate pituitary stimulation ra ther than deterioration of the pituitary mechanism for GH synthesis an d release. GHRP may also inhibit the effects of somatostatin, thus enh ancing the effects of GHRH in the old rats.