Effects of Intravenous, Subcutaneous, and Intranasal Administration of Growth Hormone (GH)-Releasing Hormone-40 on Serum GH Concentrations in Normal Men*

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Abstract
In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.003, 0.01, 0.03, and 0.1 µg/kg; n = 10), sc (1, 3.3, and 10 µg/kg; n = 8), or in (3,10,30, and 100 µg/kg; n = 5). No subject had any symptoms after administration of vehicle or GHRH-40. During the 2-h period after iv administration of GHRH-40, the maximal increment in serum GH levels above basal (nanograms per ml; mean ± SD) after the 0.1 µg/kg dose was 15.5 ± 10.4 compared to 2.4 ± 4.1 after vehicle (P = 0.0017). During the 3-h period after sc administration, when compared to the maximal increment in serym GH above basal after vehicle alone (10.2 ± 12.9), the maximal increments above basal in serum GH were increased after both the 3.3 µg/kg (26.2 ± 23.1; P = 0.022) and 10 µg/kg (63.6 ± 53.5; P = 0.0003) doses. During the 3-h period after in administration, when compared to the maximal increment in serum GH above basal after vehicle alone (2.8 ± 6.4), the maximal increments above basal in GH were higher after both the 30 µg/kg (18.5 ± 10.4; P = 0.0053) and 100 µg/kg (21,7 ± 8.1; P = 0.0028) doses. In addition, significant dose-response relationships were documented between the maximal increments above basal in serum GH and GHRH-40 administered by all routes. The mean (±SEM) peak plasma level of IR-GHRH (nanograms per ml) achieved after administration of 10 µg/kg GHRH-40, iv, as reported previously (66.6 ± 17.6), was approximately 60- and 500-fold higher than the mean levels in the current study after administration of the same dose sc (1.11 ± 0.39) or in (0.14 ± 0.02), respectively. In summary, although GHRH-40 stimulates GH release when administered iv, sc, or in, significantly higher doses were required using the sc and in routes to achieve responses comparable to those obtained with iv administration.

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