Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults

Johannes D Veldhuis, Leon Farhy, Arthur L. Weltman, Jonathan Kuipers, Judith Weltman, Laurie Wideman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The basic mechanisms that drive the renewal of GH pulses in the human are not understood. Recent ensemble models predict that pulse regeneration requires quenching of an ongoing GH pulse by somatostatin outflow and evocation of a new burst by rebound GHRH release. We reasoned that related principles might explain why women consistently maintain higher-amplitude GH secretory bursts than men. Accordingly, the present study tests the hypothesis that gender modulates the successive dynamics of GH feedback and escape in the morning fasting, when GH pulses are larger in women. To this end, we infused single iv pulses of recombinant human (rh) GH (0, 1, and 3 Mg/kg) in eight young men and six women on separate randomly ordered mornings fasting and quantitated serial inhibition and recovery of GH secretion by frequent sampling, immunochemiluminometry, a deconvolution procedure, and regularity analysis. Statistical contrasts revealed gender-comparable peak concentrations and kinetics of rhGH. However, women differed from men by way of: (1) 3.5- and 4.0-fold less feedback suppression of GH secretory-burst mass; (2) more irregular patterns of GH release during negative feedback; and (3) 12-and 14-fold greater postnadir rebound-like GH secretion after rhGH pulses. Mechanistic analyses based on a minimal feedback construct predicted that women generate higher endogenous secretagogue stimulation per unit somatostatin outflow than men. In summary, negative feedback induced by near-physiological GH pulses unmasks prominent gender-related contrasts in hypothalamo-pituitary autoregulation in young adults. A frugal but sufficient explanation of the ensemble outcomes is that women sustain greater hypothalamo-pituitary agonist input than men.

Original languageEnglish (US)
Pages (from-to)2874-2881
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number5
DOIs
StatePublished - May 2005

Fingerprint

Physiological Feedback
Growth Hormone
Young Adult
Feedback
Recovery
Somatostatin
Fasting
Deconvolution
Quenching
Regeneration
Sampling
Homeostasis
Kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults. / Veldhuis, Johannes D; Farhy, Leon; Weltman, Arthur L.; Kuipers, Jonathan; Weltman, Judith; Wideman, Laurie.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 5, 05.2005, p. 2874-2881.

Research output: Contribution to journalArticle

Veldhuis, Johannes D ; Farhy, Leon ; Weltman, Arthur L. ; Kuipers, Jonathan ; Weltman, Judith ; Wideman, Laurie. / Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 5. pp. 2874-2881.
@article{b235968da0f04d31875abea8e10d7484,
title = "Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults",
abstract = "The basic mechanisms that drive the renewal of GH pulses in the human are not understood. Recent ensemble models predict that pulse regeneration requires quenching of an ongoing GH pulse by somatostatin outflow and evocation of a new burst by rebound GHRH release. We reasoned that related principles might explain why women consistently maintain higher-amplitude GH secretory bursts than men. Accordingly, the present study tests the hypothesis that gender modulates the successive dynamics of GH feedback and escape in the morning fasting, when GH pulses are larger in women. To this end, we infused single iv pulses of recombinant human (rh) GH (0, 1, and 3 Mg/kg) in eight young men and six women on separate randomly ordered mornings fasting and quantitated serial inhibition and recovery of GH secretion by frequent sampling, immunochemiluminometry, a deconvolution procedure, and regularity analysis. Statistical contrasts revealed gender-comparable peak concentrations and kinetics of rhGH. However, women differed from men by way of: (1) 3.5- and 4.0-fold less feedback suppression of GH secretory-burst mass; (2) more irregular patterns of GH release during negative feedback; and (3) 12-and 14-fold greater postnadir rebound-like GH secretion after rhGH pulses. Mechanistic analyses based on a minimal feedback construct predicted that women generate higher endogenous secretagogue stimulation per unit somatostatin outflow than men. In summary, negative feedback induced by near-physiological GH pulses unmasks prominent gender-related contrasts in hypothalamo-pituitary autoregulation in young adults. A frugal but sufficient explanation of the ensemble outcomes is that women sustain greater hypothalamo-pituitary agonist input than men.",
author = "Veldhuis, {Johannes D} and Leon Farhy and Weltman, {Arthur L.} and Jonathan Kuipers and Judith Weltman and Laurie Wideman",
year = "2005",
month = "5",
doi = "10.1210/jc.2004-1363",
language = "English (US)",
volume = "90",
pages = "2874--2881",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "5",

}

TY - JOUR

T1 - Gender modulates sequential suppression and recovery of pulsatile growth hormone secretion by physiological feedback signals in young adults

AU - Veldhuis, Johannes D

AU - Farhy, Leon

AU - Weltman, Arthur L.

AU - Kuipers, Jonathan

AU - Weltman, Judith

AU - Wideman, Laurie

PY - 2005/5

Y1 - 2005/5

N2 - The basic mechanisms that drive the renewal of GH pulses in the human are not understood. Recent ensemble models predict that pulse regeneration requires quenching of an ongoing GH pulse by somatostatin outflow and evocation of a new burst by rebound GHRH release. We reasoned that related principles might explain why women consistently maintain higher-amplitude GH secretory bursts than men. Accordingly, the present study tests the hypothesis that gender modulates the successive dynamics of GH feedback and escape in the morning fasting, when GH pulses are larger in women. To this end, we infused single iv pulses of recombinant human (rh) GH (0, 1, and 3 Mg/kg) in eight young men and six women on separate randomly ordered mornings fasting and quantitated serial inhibition and recovery of GH secretion by frequent sampling, immunochemiluminometry, a deconvolution procedure, and regularity analysis. Statistical contrasts revealed gender-comparable peak concentrations and kinetics of rhGH. However, women differed from men by way of: (1) 3.5- and 4.0-fold less feedback suppression of GH secretory-burst mass; (2) more irregular patterns of GH release during negative feedback; and (3) 12-and 14-fold greater postnadir rebound-like GH secretion after rhGH pulses. Mechanistic analyses based on a minimal feedback construct predicted that women generate higher endogenous secretagogue stimulation per unit somatostatin outflow than men. In summary, negative feedback induced by near-physiological GH pulses unmasks prominent gender-related contrasts in hypothalamo-pituitary autoregulation in young adults. A frugal but sufficient explanation of the ensemble outcomes is that women sustain greater hypothalamo-pituitary agonist input than men.

AB - The basic mechanisms that drive the renewal of GH pulses in the human are not understood. Recent ensemble models predict that pulse regeneration requires quenching of an ongoing GH pulse by somatostatin outflow and evocation of a new burst by rebound GHRH release. We reasoned that related principles might explain why women consistently maintain higher-amplitude GH secretory bursts than men. Accordingly, the present study tests the hypothesis that gender modulates the successive dynamics of GH feedback and escape in the morning fasting, when GH pulses are larger in women. To this end, we infused single iv pulses of recombinant human (rh) GH (0, 1, and 3 Mg/kg) in eight young men and six women on separate randomly ordered mornings fasting and quantitated serial inhibition and recovery of GH secretion by frequent sampling, immunochemiluminometry, a deconvolution procedure, and regularity analysis. Statistical contrasts revealed gender-comparable peak concentrations and kinetics of rhGH. However, women differed from men by way of: (1) 3.5- and 4.0-fold less feedback suppression of GH secretory-burst mass; (2) more irregular patterns of GH release during negative feedback; and (3) 12-and 14-fold greater postnadir rebound-like GH secretion after rhGH pulses. Mechanistic analyses based on a minimal feedback construct predicted that women generate higher endogenous secretagogue stimulation per unit somatostatin outflow than men. In summary, negative feedback induced by near-physiological GH pulses unmasks prominent gender-related contrasts in hypothalamo-pituitary autoregulation in young adults. A frugal but sufficient explanation of the ensemble outcomes is that women sustain greater hypothalamo-pituitary agonist input than men.

UR - http://www.scopus.com/inward/record.url?scp=18844452380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18844452380&partnerID=8YFLogxK

U2 - 10.1210/jc.2004-1363

DO - 10.1210/jc.2004-1363

M3 - Article

VL - 90

SP - 2874

EP - 2881

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 5

ER -