The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: Dose-response relationships
| Autor: | Michael O. Thorner, J. Rivier, Donald L. Kaiser, Robert L Burke, William S. Evans, W. Vale, Mary Lee Vance |
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| Rok vydání: | 1986 |
| Předmět: |
Adult
Male medicine.medical_specialty Injections Subcutaneous Hypothalamus Peptide Stimulation Growth Hormone-Releasing Hormone Internal medicine Humans Medicine Pharmacology (medical) Adverse effect Sermorelin Administration Intranasal Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug business.industry Middle Aged Growth hormone–releasing hormone Peptide Fragments Growth hormone secretion Amino acid Endocrinology chemistry Growth Hormone Injections Intravenous Nasal administration business Linear growth |
| Zdroj: | Clinical Pharmacology and Therapeutics. 40:627-633 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/clpt.1986.237 |
| Popis: | A 29 amino acid analog of growth hormone releasing hormone (GH-RH)-40 was given intravenously, subcutaneously, and intranasally to normal men to determine its effectiveness in stimulating growth hormone (GH) release. The GH-RH analog, [Nle27]GH-RH(l-29)-NH2, is an amidated 29 amino acid peptide that has one amino acid substitution at position 27. This peptide stimulates GH secretion when given by the intravenous, subcutaneous, and intranasal routes without adverse effect. The degree of GH stimulation was variable among subjects and the greatest amount of stimulation occurred with the highest doses. GH stimulation occurred in a dose-responsive manner after all three routes of administration. A tenfold higher subcutaneous dose was required to stimulate a comparable amount of GH secretion as compared with intravenous administration, and a thirtyfold higher intranasal than intravenous dose was required to stimulate approximately one fifth the amount of GH release. For comparison, one dose of GH-RH-40, 1 µg/kg, was administered intravenously. GH secretion after 1 µg/kg GH-RH-40 and 1 µg/kg Nle27 GH-RH was comparable between the two groups of subjects. Stimulation of GH secretion by Nle27 GH-RH occurred within 5 minutes of intravenous and within 10 minutes of subcutaneous and intranasal administration; peak GH levels were observed within 30 minutes. GH levels declined and returned to near baseline levels 2 hours after administration of the analog. Since GH-RH-40 has been demonstrated to be effective in stimulating GH release and promoting acceleration of linear growth in GH-deficient children, it is likely that a shorter peptide with full biologic activity such as Nle27 GH-RH may also be effective in the treatment of some children with GH deficiency. Clinical Pharmacology and Therapeutics (1986) 40, 627–633; doi:10.1038/clpt.1986.237 |
| Databáze: | OpenAIRE |
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