Acute dexamethasone administration enhances GH responsiveness to GH releasing peptide-6 (GHRP-6) in man

OBJECTIVE Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP‐6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatost...

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Veröffentlicht in:Clinical endocrinology (Oxford) 1999-10, Vol.51 (4), p.409-414
Hauptverfasser: Pinto, Ana-Cláudia A. R., Finamor Jr, Francisco E., Lengyel, Ana-Maria J.
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creator Pinto, Ana-Cláudia A. R.
Finamor Jr, Francisco E.
Lengyel, Ana-Maria J.
description OBJECTIVE Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP‐6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatostatin release. The aim of this study was to evaluate the effect of acute dexamethasone administration on GH responsiveness to GHRP‐6 in man. DESIGN One group of subjects received iv GHRP‐6 (1 μg/kg), GH‐releasing hormone (GHRH; 100 μg), GHRH plus GHRP‐6 or saline 3.5 h after oral acute dexamethasone administration (4 mg; at 0600 h). A second study group was treated with GHRP‐6, GHRH or GHRP‐6 plus GHRH after placebo ingestion, following the same protocol. PATIENTS Sixteen normal subjects (mean age: 29 ± 3.3 years), with normal BMI (22.4 ± 2.0 kg/m2), were studied. Eight subjects received dexamethasone and the other eight were treated with placebo. MEASUREMENTS Serum GH was measured by a two site monoclonal antibody immunofluorometric assay. RESULTS In the placebo‐treated subjects, mean peak GH (mU/l; mean ± SE) and AUC (mU.min/l) values after GHRP‐6 administration (peak: 43.8 ± 9.0; AUC: 2262.0 ± 459.2) did not differ from those observed after GHRH injection (peak: 49.8 ± 12.0; AUC: 2903.4 ± 872.6). The association of the two peptides markedly increased GH levels (peak: 172.4 ± 34.2; AUC: 10393.0 ± 1894.8) compared with the isolated administration of GHRP‐6 or GHRH. In the subjects who received dexamethasone 3.5 h before saline injection, GH baseline values were significantly higher than those observed after 90 min of sampling (12.4 ± 9.4 vs. 4.6 ± 2.0). Mean GH peak and AUC values after GHRP‐6 (peak: 78.8 ± 11.0; AUC: 4114.6 ± 588.2) and after GHRH administration (peak: 46.8 ± 16.0; AUC: 3006.8 ± 1010.0) did not differ significantly in the dexamethasone‐treated subjects. In this study group, the administration of the two peptides together caused a significant increase in both peak (119.2 ± 16.0) and AUC values (7377.0 ± 937.2) compared with the response obtained after each peptide alone. When the two groups were compared, a significant increase in GH responsiveness to GHRP‐6 was observed after dexamethasone administration compared with placebo. No differences in GH response to GHRH, or to the administration of the two peptides together, were seen between the two groups. CONCLUSIONS Oral dexamethasone, at a dose of 4 mg, enhances GH releasing peptide‐6‐induced GH
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R. ; Finamor Jr, Francisco E. ; Lengyel, Ana-Maria J.</creator><creatorcontrib>Pinto, Ana-Cláudia A. R. ; Finamor Jr, Francisco E. ; Lengyel, Ana-Maria J.</creatorcontrib><description>OBJECTIVE Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP‐6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatostatin release. The aim of this study was to evaluate the effect of acute dexamethasone administration on GH responsiveness to GHRP‐6 in man. DESIGN One group of subjects received iv GHRP‐6 (1 μg/kg), GH‐releasing hormone (GHRH; 100 μg), GHRH plus GHRP‐6 or saline 3.5 h after oral acute dexamethasone administration (4 mg; at 0600 h). A second study group was treated with GHRP‐6, GHRH or GHRP‐6 plus GHRH after placebo ingestion, following the same protocol. PATIENTS Sixteen normal subjects (mean age: 29 ± 3.3 years), with normal BMI (22.4 ± 2.0 kg/m2), were studied. Eight subjects received dexamethasone and the other eight were treated with placebo. MEASUREMENTS Serum GH was measured by a two site monoclonal antibody immunofluorometric assay. RESULTS In the placebo‐treated subjects, mean peak GH (mU/l; mean ± SE) and AUC (mU.min/l) values after GHRP‐6 administration (peak: 43.8 ± 9.0; AUC: 2262.0 ± 459.2) did not differ from those observed after GHRH injection (peak: 49.8 ± 12.0; AUC: 2903.4 ± 872.6). The association of the two peptides markedly increased GH levels (peak: 172.4 ± 34.2; AUC: 10393.0 ± 1894.8) compared with the isolated administration of GHRP‐6 or GHRH. In the subjects who received dexamethasone 3.5 h before saline injection, GH baseline values were significantly higher than those observed after 90 min of sampling (12.4 ± 9.4 vs. 4.6 ± 2.0). Mean GH peak and AUC values after GHRP‐6 (peak: 78.8 ± 11.0; AUC: 4114.6 ± 588.2) and after GHRH administration (peak: 46.8 ± 16.0; AUC: 3006.8 ± 1010.0) did not differ significantly in the dexamethasone‐treated subjects. In this study group, the administration of the two peptides together caused a significant increase in both peak (119.2 ± 16.0) and AUC values (7377.0 ± 937.2) compared with the response obtained after each peptide alone. When the two groups were compared, a significant increase in GH responsiveness to GHRP‐6 was observed after dexamethasone administration compared with placebo. No differences in GH response to GHRH, or to the administration of the two peptides together, were seen between the two groups. CONCLUSIONS Oral dexamethasone, at a dose of 4 mg, enhances GH releasing peptide‐6‐induced GH release when administered 3.5 h earlier. These results suggest that dexamethasone and GHRP‐6 could act at different sites of GH releasing mechanisms. 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R.</creatorcontrib><creatorcontrib>Finamor Jr, Francisco E.</creatorcontrib><creatorcontrib>Lengyel, Ana-Maria J.</creatorcontrib><title>Acute dexamethasone administration enhances GH responsiveness to GH releasing peptide-6 (GHRP-6) in man</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clinical Endocrinology</addtitle><description>OBJECTIVE Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP‐6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatostatin release. The aim of this study was to evaluate the effect of acute dexamethasone administration on GH responsiveness to GHRP‐6 in man. DESIGN One group of subjects received iv GHRP‐6 (1 μg/kg), GH‐releasing hormone (GHRH; 100 μg), GHRH plus GHRP‐6 or saline 3.5 h after oral acute dexamethasone administration (4 mg; at 0600 h). A second study group was treated with GHRP‐6, GHRH or GHRP‐6 plus GHRH after placebo ingestion, following the same protocol. PATIENTS Sixteen normal subjects (mean age: 29 ± 3.3 years), with normal BMI (22.4 ± 2.0 kg/m2), were studied. Eight subjects received dexamethasone and the other eight were treated with placebo. MEASUREMENTS Serum GH was measured by a two site monoclonal antibody immunofluorometric assay. RESULTS In the placebo‐treated subjects, mean peak GH (mU/l; mean ± SE) and AUC (mU.min/l) values after GHRP‐6 administration (peak: 43.8 ± 9.0; AUC: 2262.0 ± 459.2) did not differ from those observed after GHRH injection (peak: 49.8 ± 12.0; AUC: 2903.4 ± 872.6). The association of the two peptides markedly increased GH levels (peak: 172.4 ± 34.2; AUC: 10393.0 ± 1894.8) compared with the isolated administration of GHRP‐6 or GHRH. In the subjects who received dexamethasone 3.5 h before saline injection, GH baseline values were significantly higher than those observed after 90 min of sampling (12.4 ± 9.4 vs. 4.6 ± 2.0). Mean GH peak and AUC values after GHRP‐6 (peak: 78.8 ± 11.0; AUC: 4114.6 ± 588.2) and after GHRH administration (peak: 46.8 ± 16.0; AUC: 3006.8 ± 1010.0) did not differ significantly in the dexamethasone‐treated subjects. In this study group, the administration of the two peptides together caused a significant increase in both peak (119.2 ± 16.0) and AUC values (7377.0 ± 937.2) compared with the response obtained after each peptide alone. When the two groups were compared, a significant increase in GH responsiveness to GHRP‐6 was observed after dexamethasone administration compared with placebo. No differences in GH response to GHRH, or to the administration of the two peptides together, were seen between the two groups. CONCLUSIONS Oral dexamethasone, at a dose of 4 mg, enhances GH releasing peptide‐6‐induced GH release when administered 3.5 h earlier. These results suggest that dexamethasone and GHRP‐6 could act at different sites of GH releasing mechanisms. Further studies are necessary to elucidate these findings.</description><subject>Adult</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Dexamethasone</subject><subject>Female</subject><subject>Glucocorticoids</subject><subject>Growth Hormone - blood</subject><subject>Growth Hormone - metabolism</subject><subject>Growth Hormone-Releasing Hormone</subject><subject>Hormones. Endocrine system</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Oligopeptides</subject><subject>Pharmacology. 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R. ; Finamor Jr, Francisco E. ; Lengyel, Ana-Maria J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4582-daaef87477d720ecdcc03b6992e142bff561415780cd5826badde4280ae35233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adult</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Dexamethasone</topic><topic>Female</topic><topic>Glucocorticoids</topic><topic>Growth Hormone - blood</topic><topic>Growth Hormone - metabolism</topic><topic>Growth Hormone-Releasing Hormone</topic><topic>Hormones. Endocrine system</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Oligopeptides</topic><topic>Pharmacology. Drug treatments</topic><topic>Tropical medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pinto, Ana-Cláudia A. R.</creatorcontrib><creatorcontrib>Finamor Jr, Francisco E.</creatorcontrib><creatorcontrib>Lengyel, Ana-Maria J.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pinto, Ana-Cláudia A. R.</au><au>Finamor Jr, Francisco E.</au><au>Lengyel, Ana-Maria J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute dexamethasone administration enhances GH responsiveness to GH releasing peptide-6 (GHRP-6) in man</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clinical Endocrinology</addtitle><date>1999-10</date><risdate>1999</risdate><volume>51</volume><issue>4</issue><spage>409</spage><epage>414</epage><pages>409-414</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract>OBJECTIVE Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP‐6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatostatin release. The aim of this study was to evaluate the effect of acute dexamethasone administration on GH responsiveness to GHRP‐6 in man. DESIGN One group of subjects received iv GHRP‐6 (1 μg/kg), GH‐releasing hormone (GHRH; 100 μg), GHRH plus GHRP‐6 or saline 3.5 h after oral acute dexamethasone administration (4 mg; at 0600 h). A second study group was treated with GHRP‐6, GHRH or GHRP‐6 plus GHRH after placebo ingestion, following the same protocol. PATIENTS Sixteen normal subjects (mean age: 29 ± 3.3 years), with normal BMI (22.4 ± 2.0 kg/m2), were studied. Eight subjects received dexamethasone and the other eight were treated with placebo. MEASUREMENTS Serum GH was measured by a two site monoclonal antibody immunofluorometric assay. RESULTS In the placebo‐treated subjects, mean peak GH (mU/l; mean ± SE) and AUC (mU.min/l) values after GHRP‐6 administration (peak: 43.8 ± 9.0; AUC: 2262.0 ± 459.2) did not differ from those observed after GHRH injection (peak: 49.8 ± 12.0; AUC: 2903.4 ± 872.6). The association of the two peptides markedly increased GH levels (peak: 172.4 ± 34.2; AUC: 10393.0 ± 1894.8) compared with the isolated administration of GHRP‐6 or GHRH. In the subjects who received dexamethasone 3.5 h before saline injection, GH baseline values were significantly higher than those observed after 90 min of sampling (12.4 ± 9.4 vs. 4.6 ± 2.0). Mean GH peak and AUC values after GHRP‐6 (peak: 78.8 ± 11.0; AUC: 4114.6 ± 588.2) and after GHRH administration (peak: 46.8 ± 16.0; AUC: 3006.8 ± 1010.0) did not differ significantly in the dexamethasone‐treated subjects. In this study group, the administration of the two peptides together caused a significant increase in both peak (119.2 ± 16.0) and AUC values (7377.0 ± 937.2) compared with the response obtained after each peptide alone. When the two groups were compared, a significant increase in GH responsiveness to GHRP‐6 was observed after dexamethasone administration compared with placebo. No differences in GH response to GHRH, or to the administration of the two peptides together, were seen between the two groups. CONCLUSIONS Oral dexamethasone, at a dose of 4 mg, enhances GH releasing peptide‐6‐induced GH release when administered 3.5 h earlier. These results suggest that dexamethasone and GHRP‐6 could act at different sites of GH releasing mechanisms. Further studies are necessary to elucidate these findings.</abstract><cop>Oxford BSL</cop><pub>Blackwell Science Ltd</pub><pmid>10583306</pmid><doi>10.1046/j.1365-2265.1999.00792.x</doi><tpages>6</tpages></addata></record>
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subjects Adult
Area Under Curve
Biological and medical sciences
Dexamethasone
Female
Glucocorticoids
Growth Hormone - blood
Growth Hormone - metabolism
Growth Hormone-Releasing Hormone
Hormones. Endocrine system
Humans
Male
Medical sciences
Oligopeptides
Pharmacology. Drug treatments
Tropical medicine
title Acute dexamethasone administration enhances GH responsiveness to GH releasing peptide-6 (GHRP-6) in man
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