Precisely how ageing and/or androgen deficiency impacts the GH/IGF1 neuroregulatory unit is not known (Giustina & Veldhuis 1998). However, both animal and human studies make an ensemble perspective essential. For example, clinically, only L-arginine (an agent believed to withdraw SS) combined with (a) GHRH, (b) GHRP or (c) both GHRH and GHRP can normalize GH secretion acutely, when judged against similarly stimulated young adults (Ghigo et al 1990, Khorram et al 1997, Veldhuis & Giustina 2000). Specifically, no single GHRH or GHRP agonist, or SS antagonist, can restore GH/IGF1 output completely in older volunteers (Veldhuis & Giustina 2000, degli Uberti et al 1997, Giustina & Veldhuis 1998). Notably, sustained exogenous GHRH stimulation or GHRP2 drive only partially reconstitutes the GH/IGF1 axis in elderly humans, thus pointing to a relative deficiency of each agonist (Corpas et al 1992, Evans et al 2000, Iranmanesh et al 1998, Khorram et al 1997). However, the GH-stimulating effect of GHRH infused i.v. over 3 days is blunted by increasing age and relative hypoandrogenaemia (Iranmanesh et al 1998; Fig. 4).
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