Complementary secretagogue pairs unmask prominent gender-related contrasts in mechanisms of growth hormone pulse renewal in young adults

Cacia Soares-Welch, Leon Farhy, Kristi L. Mielke, Farid H. Mahmud, John M. Miles, Cyril Y. Bowers, Johannes D Veldhuis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The present study examines the thesis that pulsatile GH secretion is controlled simultaneously by three principal signals; viz., GHRH, GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS). According to this ensemble notion, no single regulatory peptide acts alone or can be interpreted in isolation. Therefore, to investigate gender-specific control of pulsatile GH secretion, we designed dual-effector stimulation paradigms in eight young men and six women as follows: 1) L-arginine/GHRH (to clamp low SS and high GHRH input); 2) L-arginine/GHRP-2 (to clamp low SS and high GHRP drive); 3) GHRH/GHRP-2 (to clamp high GHRH and high GHRP feed-forward); vs. 4) saline (unclamped). Statistical comparisons revealed that: 1) fasting pulsatile GH secretion was 7.6-fold higher in women than men (P < 0.001); 2) L-arginine/GHRH and L-arginine/GHRP-2 evoked, respectively, 4.6- and 2.2-fold greater burst-like GH release in women than men (P < 0.001 and P = 0.015); and 3) GHRH/GHRP-2 elicited comparable GH secretion by gender. In the combined cohorts, estradiol concentrations positively predicted responses to L-arginine/ GHRP-2 (r2 = 0.40, P = 0.005), whereas testosterone negatively predicted those to L-arginine/GHRH (r2 = 0.56, P = 0.002). Based upon a simplified biomathematical model of three-peptide control, the current outcomes suggest that women maintain greater GHRH potency, GHRP efficacy, and opposing SS outflow than men. This inference upholds recent clinical precedence and yields valid predictions of sex differences in self-renewable GH pulsatility.

Original languageEnglish (US)
Pages (from-to)2225-2232
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number4
DOIs
StatePublished - Apr 2005

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Growth Hormone
Arginine
Young Adult
Somatostatin
Clamping devices
glycyl-histidyl-arginyl-proline
Peptides
Ghrelin
Sex Characteristics
Testosterone
Estradiol
Fasting
growth hormone-releasing peptide-2

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Complementary secretagogue pairs unmask prominent gender-related contrasts in mechanisms of growth hormone pulse renewal in young adults. / Soares-Welch, Cacia; Farhy, Leon; Mielke, Kristi L.; Mahmud, Farid H.; Miles, John M.; Bowers, Cyril Y.; Veldhuis, Johannes D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 4, 04.2005, p. 2225-2232.

Research output: Contribution to journalArticle

Soares-Welch, Cacia ; Farhy, Leon ; Mielke, Kristi L. ; Mahmud, Farid H. ; Miles, John M. ; Bowers, Cyril Y. ; Veldhuis, Johannes D. / Complementary secretagogue pairs unmask prominent gender-related contrasts in mechanisms of growth hormone pulse renewal in young adults. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 4. pp. 2225-2232.
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