THE EFFECTS OF BETA(1)-ADRENERGIC BLOCKADE ON THE GROWTH-RESPONSE TO GROWTH-HORMONE (GH)-RELEASING HORMONE-THERAPY IN GH-DEFICIENT CHILDREN

Acute suppression of SRIH secretion with a beta-adrenergic antagonist can increase the GH response to GHRH. To determine whether chronic bet a-blockade could enhance the growth-promoting effects of GHRH therapy, we conducted a double blind, placebo-controlled, randomized, cross-ov er trial of coadministration of the selective beta(1)-antagonist ateno lol together with GHRH in 11 GH-deficient children. In randomly chosen order, each patient received two 12-month treatment periods with a si ngle daily injection of GHRH (20 mu g/kg, sc, at bedtime), plus daily oral administration of either atenolol (1 mg/kg) or placebo. The growt h velocity increased, rising from a mean +/- SD of 2.6 +/- 0.4 cm/yr b efore treatment to 5.4 +/- 1.0 cm/yr during the first year of treatmen t with GHRH plus placebo and to 6.8 +/- 1.2 cm/yr during the first yea r of treatment with GHRH plus atenolol. The mean growth velocity durin g treatment with GHRH plus atenolol was significantly greater than tha t observed during GHRH plus placebo (P < 0.05). After cross-over, howe ver, during the second year of therapy, we did not observe any signifi cant differences in growth velocity between the two groups (4.2 +/- 1. 4 us. 3.9 +/- 0.8 cm/yr during treatment with GHRH plus placebo and GH RH plus atenolol, respectively). The mean 24-h serum GH levels were 1. 4 +/- 0.9 mu g/L during the baseline period, 1.3 +/- 0.2 and 2.0 +/- 1 .4 mu g/L during the first year of GHRH plus placebo and GHRH plus ate nolol, respectively (P = NS), and 2.7 +/- 1.4 and 1.4 +/- 0.4 mu g/L d uring the second year of GHRH plus placebo and GHRH plus atenolol, res pectively (P < 0.05). This is the first demonstration that alteration of neurotransmitter action can enhance the therapeutic response to a h ypothalamic releasing factor.