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Insights Into A Role Of GH Secretagogues In Reversing The Age-related Decline In The GH/IGF-I Axis.

Miriam García-San Frutos, L. Cacicedo, C. Fernández, D. Vicent, Beatriz Velasco, Helena Zapatero, F. Sánchez-Franco
Published 2007 · Biology, Medicine

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Growth hormone (GH) secretion and serum insulin-like growth factor-I (IGF-I) decline with aging. This study addresses the role played by the hypothalamic regulators in the aging GH decline and investigates the mechanisms through which growth hormone secretagogues (GHS) activate GH secretion in the aging rats. Two groups of male Wistar rats were studied: young-adult (3 mo) and old (24 mo). Hypothalamic growth hormone-releasing hormone (GHRH) mRNA and immunoreactive (IR) GHRH dramatically decreased (P < 0.01 and P < 0.001) in the old rats, as did median eminence IR-GHRH. Decreases of hypothalamic IR-somatostatin (SS; P < 0.001) and SS mRNA (P < 0.01), and median eminence IR-SS were found in old rats as were GHS receptor and IGF-I mRNA (P < 0.01 and P < 0.05). Hypothalamic IGF-I receptor mRNA and protein were unmodified. Both young and old pituitary cells, cultured alone or cocultured with fetal hypothalamic cells, responded to ghrelin. Only in the presence of fetal hypothalamic cells did ghrelin elevate the age-related decrease of GH secretion to within normal adult range. In old rats, growth hormone-releasing peptide-6 returned the levels of GH and IGF-I secretion and liver IGF-I mRNA, and partially restored the lower pituitary IR-GH and GH mRNA levels to those of young untreated rats. These results suggest that the aging GH decline may result from decreased GHRH function rather than from increased SS action. The reduction of hypothalamic GHS-R gene expression might impair the action of ghrelin on GH release. The role of IGF-I is not altered. The aging GH/IGF-I axis decline could be rejuvenated by GHS treatment.
This paper references
Neural control of somatotropic function.
E. Müller (1987)
Biosynthesis of growth hormone-releasing factor by fetal rat cerebrocortical and hypothalamic cells
Gumersindo Fernández Vázquez (1994)
Human growth hormone and cortisol response to insulin stimulation in aging.
M. Muggeo (1975)
Secretagogues and the somatotrope: signaling and proliferation.
L. Frohman (2000)
Effects of aging and dietary restriction on tissue protein synthesis: relationship to plasma insulin-like growth factor-1.
W. Sonntag (1992)
Dynamics of growth hormone responsiveness to growth hormone releasing factor in aging rats: peripheral and central influences.
N. Deslauriers (1991)
Delayed Age-Associated Decrease in Growth Hormone Pulsatile Secretion and Increased Orexigenic Peptide Expression in the Lou C/Jall Rat
L. Kappeler (2004)
Alterations in Hypothalamic Insulin‐Like Growth Factor‐I and its Associations with Gonadotropin Releasing Hormone Neurones During Reproductive Development and Ageing
B. H. Miller (2001)
Growth hormone (GH) and GH-releasing peptide-6 increase brain insulin-like growth factor-I expression and activate intracellular signaling pathways involved in neuroprotection.
L. Frago (2002)
Moderate caloric restriction alters the subcellular distribution of somatostatin mRNA and increases growth hormone pulse amplitude in aged animals.
W. Sonntag (1995)
Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary.
M. Berelowitz (1981)
Increased secretion of somatostatin-28 from hypothalamic neurons of aged rats in vitro
W. Sonntag (1986)
Sex differentiation of growth hormone-releasing hormone and somatostatin neurons in the mouse hypothalamus: an immunohistochemical and morphological study
Nurhidayat (1999)
Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients.
A. Rigamonti (2002)
Neuroendocrine control of growth hormone secretion
E. Mueller (2004)
Age-related changes in growth hormone releasing factor and somatostatin in the rat
N Morimoto (1988)
Growth hormone and aging: Regulation, signal transduction and replacement therapy
X. Xu (1996)
Age-related changes in growth hormone releasing factor and somatostatin in the rat hypothalamus.
N. Morimoto (1988)
Defective hypothalamic growth hormone (GH)-releasing hormone activity may contribute to declining GH secretion with age in man.
E. D. degli Uberti (1997)
Sensitivity to exogenous GH and reversibility of the reduced IGF-I gene expression in aging rats.
B. Velasco (2001)
Advances in male contraception.
S. Page (2008)
Effects of human growth hormone in men over 60 years old.
D. Rudman (1990)
Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta
KJ Livak (2001)
Ghrelin acts in the central nervous system to stimulate gastric acid secretion.
Y. Date (2001)
Role of naloxone and opioid peptides on thyrotrophin, alpha subunit and beta thyrotrophin by dispersed rat pituitary cells.
L. Cacicedo (1985)
Somatostatin gene expression in hypothalamus and cortex of aging male rats
W. Sonntag (1990)
Alterations in stomach ghrelin production and in ghrelin-induced growth hormone secretion in the aged rat
E. Englander (2004)
Regulation of Pit-1 expression by ghrelin and GHRP-6 through the GH secretagogue receptor.
A. Garcia (2001)
Growth Hormone‐Releasing Hormone Receptor (GNRH‐R) and Growth Hormone Secretagogue Receptor (GHS‐R) mRNA Levels During Postnatal Development in Male and Female Rats
Kamegai (1999)
The Hypothalamic Mechanisms of the Hypophysiotropic Action of Ghrelin
A. Wren (2002)
Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level.
V. Popović (1995)
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
K. Livak (2001)
Reduced growth hormone releasing factor (GHRF)-like immunoreactivity and GHRF gene expression in the hypothalamus of aged rats
V. D. G. Colonna (1989)
Growth hormone induces somatostatin and insulin-like growth factor I gene expression in the cerebral hemispheres of aging rats.
J. López-Fernández (1996)
Growth Hormone, Body Composition, and Aging
D. Rudman (1985)
Ghrelin acts in the central nervous system to stimulate E1150 SECRETAGOGUES AND GH SECRETION DECLINE IN AGING RATS AJP-Endocrinol Metab
Y Date (2007)
Elements in the pathophysiology of diminished growth hormone (GH) secretion in aging humans
J. Veldhuis (2007)
Chronic bromocriptine administration restores luteinizing hormone response to naloxone in postmenopausal women.
G. Melis (1988)
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
M. Kojima (1999)
Physiological role of somatostatin in regulation of pulsatile growth hormone secretion.
G. Tannenbaum (1985)
Growth hormone-releasing factor production by fetal rat cerebrocortical and hypothalamic cells in primary culture.
G. Fernández (1989)
Selective alteration at the growth‐hormone‐ releasing‐hormone nerve terminals during aging in GHRH‐green fluorescent protein mice
G. Alonso (2007)
Contents Vol. 47, 2001
T. Bruzzese (2001)
Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats
D. Olchovsky (1993)
Growth Hormone Therapy in Adults
F. Conceição (2001)
Hormonal regulation of rat hypothalamic neuropeptide mRNAs: effect of hypophysectomy and hormone replacement on growth-hormone-releasing factor, somatostatin and the insulin-like growth factors.
T. Wood (1991)
Growth hormone gene expression and secretion in aging rats is age dependent and not age-associated weight increase related.
B. Velasco (1998)
A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release
A. Howard (1996)
Increased pituitary response to somatostatin in aging male rats: relationship to somatostatin receptor number and affinity.
K. Spik (1989)
Pituitary growth hormone and hypothalamic somatostatin in young female rats versus old constant estrous female rats
L. J. Forman (2005)
Growth hormone-releasing hormone, somatostatin, galanin and β-endorphin afferents to the hypothalamic periventricular nucleus
M. Fodor (1994)
High plasma concentrations of human atrial natriuretic polypeptide in aged men.
M. Ohashi (1987)
Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats.
J. Kamegai (1999)
Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults.
S. Teichman (2006)
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse.
M. Alba (2006)
Effect of long-term administration of Hexarelin on the somatotrophic axis in aged rats.
L. Cattaneo (1997)
Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland.
M. Parenti (1991)
Decreased pulsatile release of growth hormone in old male rats.
W. Sonntag (1980)
Pituitary alterations involved in the decline of growth hormone gene expression in the pituitary of aging rats.
M. G. S. Frutos (2007)
The Rat Brain in Stereotaxic Coordinates
G. Paxinos (1983)
Impaired ability of old male rats to secrete growth hormone in vivo but not in vitro in response to hpGRF(1-44).
W. Sonntag (1983)
Effect of rat age on serum levels of growth hormone and somatomedins
J. Florini (1981)
Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin
G. Tannenbaum (2007)
Aging-related growth hormone (GH) decrease is a selective hypothalamic GH-releasing hormone pulse amplitude mediated phenomenon.
M. Russell-Aulet (2001)
Divergent Effects of Acute Depolarization on Somatostatin Release and Protein Synthesis in Cultured Fetal and Neonatal Rat Brain Cells
M. de los Frailes (1989)
Effects of CNS active drugs and somatostatin antiserum on growth hormone release in young and old male rats.
W. Sonntag (1981)
Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects.
I. Chapman (1996)
Robust growth hormone (GH) secretion in aged female rats co-administered GH-releasing hexapeptide (GHRP-6) and GH-releasing hormone (GHRH).
R. Walker (1991)
Presence of ghrelin in normal and adenomatous human pituitary
M. Korbonits (2007)
Development of growth hormone secretagogues.
R. Smith (2005)
Growth Hormone-Releasing Factorについて (視床下部のReleasing Factor(特集))
高橋 清久 (1966)
Ghrelin and growth hormone secretagogue receptor expression in mice during aging.
Y. Sun (2007)
Growth Hormone (GH) but not IGF-I-Secretion is Stimulated in Aged Rats by Chronic Hexarelin and GHRP-6 administration.
Settembrini (1998)

This paper is referenced by
Azapeptide analogues of the growth hormone releasing peptide 6 as cluster of differentiation 36 receptor ligands with reduced affinity for the growth hormone secretagogue receptor 1a.
C. Proulx (2012)
Effect of aging and oxidative stress on elongation factor-2 in hypothalamus and hypophysis
S. Argüelles (2011)
Positional scanning for peptide secondary structure by systematic solid-phase synthesis of amino lactam peptides.
A. Jamieson (2009)
The effects of ghrelin on inflammation and the immune system
Dolgor Baatar (2011)
Peripheral activities of growth hormone-releasing hormone (GHRH)
R. Granata (2018)
Chapter 3 Aging and Subclinical Thyroid Dysfunction
D. Rosenthal (2017)
Growth hormone-releasing hormone plasmid treatment by electroporation decreases offspring mortality over three pregnancies.
Ryan Person (2008)
Peripheral activities of growth hormone-releasing hormone
R. Granata (2016)
Review Article Integrating Ghs into the Ghrelin System 1. Overview
Johannes D. Veldhuis ()
Hormones and the Aging Brain
Í. Azcoitia (2012)
Age-related changes of GH-IGF1 axis function
G. Mazzoccoli (2011)
Role of endogenous somatostatin in regulating GH output under basal conditions and in response to metabolic extremes
R. M. Luque (2008)
Sistema GH-IGFI y envejecimiento cerebral
L. Cacicedo (2010)
Structure–Activity Analysis of the Growth Hormone Secretagogue GHRP‐6 by α‐ and β‐Amino γ‐Lactam Positional Scanning
Nicolas Boutard (2010)
Aging and Oxidative Stress Decrease Pineal Elongation Factor 2: In Vivo Protective Effect of Melatonin in Young Rats Treated With Cumene Hydroperoxide
M. Muñoz (2017)
Integrating GHS into the Ghrelin System
J. Veldhuis (2010)
Endocrinological derangements in COPD
F. Laghi (2009)
Aging and Subclinical Thyroid Dysfunction
C. Costa (2013)
Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1
N. Fujitsuka (2016)
Proliferative and protective effects of the GH/IGF-I axis on cardiomyocytes and neural progenitor cells
I. Johansson (2008)
Méthodologie pour la synthèse combinatoire d’azapeptides: application à la synthèse d’analogues aza-GHRP-6 en tant que ligands du récepteur CD36
C. Proulx (2012)
Rejuvenation of the Aging Thymus : Growth Hormone-and Ghrelin-Mediated Signaling Pathways
D. Taub (2010)
Effects of maternal plasmid GHRH treatment on offspring growth.
A. Khan (2010)
Acromegaly and aging: a comparative cross-sectional study.
E. Hatipoğlu (2015)
Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways.
D. Taub (2010)
WITHDRAWN: Neuroendocrine axes function in healthy aging: Evaluation of predictive and manipulable blood serum indexes.
G. Mazzoccoli (2010)
[The GH-IGF-I system and cerebral aging].
L. Cacicedo (2010)
Long-term dietary restriction influences plasma ghrelin and GOAT mRNA level in rats
R. Reimer (2010)
Growth hormone-releasing hormone: not only a neurohormone
H. Kiaris (2011)
Neuroendocrine axes function in healthy aging: Evaluation of predictive and manipulable blood serum indexes
G. Mazzoccoli (2011)
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