Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretogogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans

Mauro Maccario, Johannes D Veldhuis, Fabio Broglio, Lidia Di Vito, Emanuela Arvat, Romano Deghenghi, Ezio Ghigo

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. Design: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 μg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 μg/kg i.v. HEX at the end of each 24-h sampling period was studied. Methods: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. Results: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. Conclusions: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.

Original languageEnglish (US)
Pages (from-to)311-318
Number of pages8
JournalEuropean Journal of Endocrinology
Volume146
Issue number3
StatePublished - 2002
Externally publishedYes

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Subcutaneous Injections
Prolactin
Adrenocorticotropic Hormone
Growth Hormone
Hydrocortisone
Insulin-Like Growth Factor I
hexarelin
Appointments and Schedules
Corticotrophs
Hormones
Lactotrophs
Injections
Entropy
Half-Life
Healthy Volunteers
Down-Regulation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretogogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans. / Maccario, Mauro; Veldhuis, Johannes D; Broglio, Fabio; Di Vito, Lidia; Arvat, Emanuela; Deghenghi, Romano; Ghigo, Ezio.

In: European Journal of Endocrinology, Vol. 146, No. 3, 2002, p. 311-318.

Research output: Contribution to journalArticle

Maccario, Mauro ; Veldhuis, Johannes D ; Broglio, Fabio ; Di Vito, Lidia ; Arvat, Emanuela ; Deghenghi, Romano ; Ghigo, Ezio. / Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretogogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans. In: European Journal of Endocrinology. 2002 ; Vol. 146, No. 3. pp. 311-318.
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abstract = "Objective: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. Design: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 μg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 μg/kg i.v. HEX at the end of each 24-h sampling period was studied. Methods: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. Results: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. Conclusions: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.",
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T1 - Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretogogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans

AU - Maccario, Mauro

AU - Veldhuis, Johannes D

AU - Broglio, Fabio

AU - Di Vito, Lidia

AU - Arvat, Emanuela

AU - Deghenghi, Romano

AU - Ghigo, Ezio

PY - 2002

Y1 - 2002

N2 - Objective: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. Design: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 μg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 μg/kg i.v. HEX at the end of each 24-h sampling period was studied. Methods: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. Results: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. Conclusions: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.

AB - Objective: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. Design: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 μg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 μg/kg i.v. HEX at the end of each 24-h sampling period was studied. Methods: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. Results: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. Conclusions: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.

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