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It is now well established that specific antibodies and binding proteins can potentiate rather than inhibit hormone activity. In order to investigate this phenomenon further, the current study was undertaken using a hormone with a characterised structure, in terms of receptor binding, and for which activity has already been manipulated in specific ways (prolongation of half-life, increased receptor affinity) using synthetic hormone analogues. GH-releasing factor (GRF) is a 40 or 44 residue peptide and is, together with somatostatin, responsible for the regulation of GH secretion. The effects of site-directed anti peptide antibodies were determined on the activity of GRF in vivoand in vitroas GH release. The peptide regions of GRF were: 1–14 (part of putative receptor-binding region) and 31–44 and 35–44 (sites thought to be distant from the receptor-binding region). Five sheep were administered GRF (1 μg/kg), anti peptide immunoglobulin (Ig; a calculated tenfold excess binding to GRF dose), or GRF together with anti peptide Ig (preincubated for 1 h). GRF induced a significant increase in plasma GH concentration over the next 240 min, this was abolished when GRF was administered with anti 1–14 Ig (P<0·05) and augmented (P<0·05) when GRF was administered with anti 35–44 Ig; anti 31–44 had no effect on GRF activity. Anti 35–44 Ig alone induced an increase in GH secretion which was equivalent to that for GRF alone, implying that the antibody had interacted and potentiated with endogenous GRF. The Ig effects on exogenous GRF activity were confirmed for GH release in vitrousing primary cultures of sheep pituitary cells, except that anti 31–44 Ig also augmented GH release (P<0·05) when co-administered with GRF. These data are compatible with current findings on the regulation of GRF activity, namely that increases in hormone activity may be achieved by at least two mechanisms: protection from degradation (decreased clearance rate) and changed hormone–receptor interaction.Journal of Endocrinology(1995) 146,535–541

Long–term administration of GH to normal, well–fed lambs caused a significant increase in net muscle growth. This could be accounted for by increased rates of muscle protein synthesis, although red and white muscles responded differently. The increased rate of protein synthesis was due to an increased protein synthetic capacity (increased muscle RNA content) but efficiency per unit of RNA also tended to increase in red muscle. For similar increases in net growth, protein turnover was increased to a much greater extent in red than in white muscle. The ratio of collagen to non–collagen protein was unaffected in both muscle types by GH treatment, even though collagen synthesis rates were significantly increased in red muscle. To date, GH is the only anabolic agent in ruminants which acts via increased rates of protein synthesis rather than by decreased rates of protein degradation.