Relationship Between Exercise and Growth Hormone GH Neuroendocrine Function Acute Exercise

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Relationship Between Exercise and Growth Hormone
(GH) Neuroendocrine FunctionAcute Exercise

• Arthur Weltman, Ph.D.
• Professor Departments of Medicine and Human
  Services
• University of Virginia
• Charlottesville, VA

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Aging and GH Release

• Growth hormone (GH) secretion declines with
  aging, and many age related changes resemble
  those of GH deficient adults
• Reduced muscle mass and exercise capacity
• Increased body fat, especially AVF
• Unfavorable lipid and lipoprotein profiles
• Reduction in bone mineral density
• Increased risk of vascular disease

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Acute Exercise and GH Secretion

• Acute physical exercise is a well known stimulus
  of GH release (Wideman et al 1999, 2000 Chang et
  al1986 Felsing et al. 1992 Kanaley et al. 1997)
• In younger men and women a linear dose response
  relationship is observed between exercise
  intensity and GH release (Pritzlaff et al 1999)
• The GH response to exercise is blunted with aging
  and in obesity (Weltman et al. 2000 Kanaley et
  al. 1998)

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Introduction

• Acute bouts of exercise increase the plasma
  concentration of GH.
• Intensity and duration of acute exercise, work
  output and muscle mass used during exercise, and
  fitness/training state may all influence in part
  the GH response to exercise.

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Introduction

• Exercise intensity may play a key role, with
  exceeding of a particular threshold of exercise
  intensity needed before a significant rise in GH
  concentration is detected.
• This threshold may correspond to the lactate
  threshold (LT) (Felsing et al., 1992 Weltman et
  al., 1992), possibly through (central)
  catecholamine release.

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PURPOSE HYPOTHESIS

• We examined the effects of exercise intensity on
  GH secretion in young men vs young women.
• We hypothesized that the GH response to exercise
  is related to exercise intensity in a linear
  pattern in young men and women.
• We also hypothesized that the magnitude of change
  in GH release with increasing exercise intensity
  will be greater in women than men.

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Mean Serum GH
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GH RELEASE AND EXERCISE INTENSITYYOUNG MALES VS
FEMALES
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Major Findings

• In both young men and women, the magnitude of GH
  release rises linearly with increasing exercise
  intensity in an apparent dose-response
  relationship.
• The magnitude of change in GH release with
  increasing exercise intensity is greater in young
  women than in young men.

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CLINICAL IMPLICATIONS

• The present data suggest that higher exercise
  training intensities will enhance daily GH
  secretion rates to a greater degree than lower
  exercise training intensities.

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The Relationship Between Exercise Intensity and
Growth Hormone (GH) Release is Attenuated in
Older Men

• A. Weltman C.J. Pritzlaff
• L. Wideman J.Y. Weltman
• R.D. Abbott M. Gutgesell
• J.D. Veldhuis M.L. Hartman
• GCRC Exercise Physiology Laboratory
• University of Virginia
• Supported in part by NIH grants RR00847 (GCRC)
  and RO1AG10997

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Introduction

• GH secretion declines with aging in both men and
  women. In men, there is a 14 decline in 24-hour
  GH production rates with each decade of
  increasing age.
• Fitness also declines with age, with a rate of
  decline in VO2max of 10 with each decade of
  increasing age.

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PURPOSE HYPOTHESIS

• We examined the effects of exercise intensity on
  GH release in young men and older men.
• We hypothesized that the GH response to exercise
  is related to exercise intensity in a linear
  pattern in young and older men.
• We also hypothesized that the magnitude of change
  in GH release with increasing exercise intensity
  will be attenuated in older men.

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GH AND EXERCISE INTENSITYYOUNG VS OLDER MALES
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MAJOR FINDINGS

• In young and older men the GH response to
  exercise was related to exercise intensity in a
  linear dose response pattern.
• However, in older men an 4-fold reduction in GH
  release was observed (vs younger men) with each
  increase in relative exercise intensity.

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CLINICAL IMPLICATIONS

• The present data suggest that higher exercise
  training intensities will enhance GH secretion
  rates to a greater degree than lower exercise
  training intensities in young men.
• However, in older men exercise alone may not
  result in a sufficient stimulus for GH release.

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CLINICAL IMPLICATIONS

• In young adults exercise augments the GH response
  to GHRP-2.
• In older adults oral administration of a GH
  secretagogue stimulates the GH-IGF-I axis.
• Perhaps a combination of exercise and an oral GH
  secretagogue may enhance GH secretion and improve
  clinical outcomes in older adults.

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Synergy of L-arginine and GHRP-2 stimulation of
growth hormone in men and women modulation by
exercise
L. Wideman, J.Y. Weltman, J.T. Patrie, C.Y.
Bowers, N. Shah, S. Story, J.D. Veldhuis, and A.
Weltman Am. J. Physiol. Integrative Comp.
Physiol. 279R1467-R1477, 2000.
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Rest
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Rest
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Exercise
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Exercise
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Conclusions

• Exercise potentiates the individual and joint
  stimulatory actions of arginine and GHRP-2 in
  both men and women

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GHRP-2 Partially Rescues Impaired Exercise
Stimulation of Growth Hormone (Gh) Release in
Older Men

• Arthur Weltman, Kimberly Brill, Judy Y. Weltman,
  Stacey M. Anderson, C.Y. Bowers, and Johannes D.
  Veldhuis
• University of Virginia

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GH Area Under the Curve(mg/L, from 0800 - 1200 h)
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Summed GH Secretory Burst Mass (above baseline,
mg/L, from 0930 - 1100 h)
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SUMMARY AND CONCLUSIONS

• The present data indicate that exercise and
  GHRP-2 act via independent stimulatory mechanisms
  to drive GH output in older men.
• However, unlike supraadditive effects observed in
  young men, combined stimulation by exercise and
  GHRP-2 may be only additive in older men.
• If corroborated, the later distinction could
  denote excessive somatostatinergic restraint
  and/or impaired outflow of endogenous GHRH
  (which synergizes with GHPRs) in aging

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Obesity attenuates the growth hormone response to
exercise (modified from Kanaley et al. J Clin
Endocrinol Metab 84 3156-3161, 1999)
6 h Integrated GH (mg/L X min)
Blood sampling at 5 min intervals 0700-0800 h
baseline 0800-0830 h exercise (70 VO2 max)
0830-1300 h recovery
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EFFECTS OF CONTINUOUS VS INTERMITTENT EXERCISE ON
CALORIC EXPENDITURE IN LEAN AND OBESE MALES

• A. Weltman, D. Watson, K.I. Frick, J.Y. Weltman,
• L. Wideman, J. Patrie, D.J. Mistry,
• S.A. Anderson, J.D. Veldhuis, and
• G.A. Gaesser
• Supported in part by a grant to the
• General Clinical Research Center
• NIH RR00847

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EFFECT OF BRIEF EXERCISE ON CIRCULATING
INSULIN-LIKE GROWTH FACTOR ICAPPON ET AL. J.
APPL. PHYSIOL. 76 2490-2496, 1994
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HUMAN GROWTH HORMONE RESPONSE TO REPEATED BOUTS
OF EXERCISEMODIFIED FROM KANALEY ET AL. J. APPL.
PHYSIOL. 83 1756-1761, 1997
1.5-h Integrated Serum GH Concentration 30 min
exercise 1-h recovery (mg/L min)
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HUMAN GROWTH HORMONE RESPONSE TO REPEATED BOUTS
OF EXERCISEMODIFIED FROM KANALEY ET AL. J.
APPL. PHYSIOL. 83 1756-1761, 1997
24-h Integrated Serum GH Concentration (mg/L
min)
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INTRODUCTION

• Recent data suggest that, at an equivalent
  cumulative exercise duration, repeated bouts of
  exercise distributed over the day may be more
  effective than a single bout of exercise in
  reducing weight, waist circumference and blood
  pressure.

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GH RESPONSES TO CONTINUOUS AND INTERMITTENT
EXERCISE

• Ten minutes of exercise above the LT stimulates
  GH release
• Repeated bouts of exercise increase 24 h GH
  release
• We hypothesized that both intermittent and
  continuous exercise would stimulate 24 h GH
  secretion and that intermittent exercise would
  result in greater 24 h GH release than continuous
  exercise

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LEAN MALES
OBESE MALES
C
C
30

30
3x10

3x10
7 am 7 pm
7 am
7 am 7 pm
7 am
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24 H GH AUC(mg/Lv min)
Lean gt Obese p 0.002 1x30 3x10 gt C p
0.005 Significant 2 way interaction, p 0.03
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GH HALF-LIFE (MIN)
Lean gt Obese p 0.02
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GH PULSE AMPLITUDE (mg/Lv)
Lean gt Obese p 0.004 1x30 3x10 gt C p
0.001 Significant 2 way interaction, p 0.01
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MASS OF GH/PULSE (mg/Lv)
Lean gt Obese p 0.002 1x30 3x10 gt C p
0.0002 Trend for significant 2 way interaction, p
0.06
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GH PRODUCTION RATE(mg/Lv min)
Lean gt Obese p 0.002
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SUMMARY

• Lean gt Obese
• 24 h GH AUC number of GH pulses GH half-life
  GH pulse amplitude Mass of GH per pulse GH
  production rate
• 1 x 30 3 x 10 gt C
• 24 h GH AUC GH pulse amplitude Mass of GH per
  pulse
• C gt 1 x 30 3 x 10
• number of GH pulses
• No differences among conditions
• GH half-life GH production rate

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CONCLUSIONS

• The GH response at rest and in response to
  exercise is blunted in young adult obese males
• Both continuous and intermittent exercise result
  in a similar augmentation in 24 h GH secretory
  patterns
• The magnitude of the GH response to exercise is
  greater in lean males than in obese males

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FUTURE DIRECTIONS

• Examine the relationship between exercise
  duration and GH secretion
• Examine the effects of continuous and
  intermittent exercise training programs on
  exercise adherence, GH secretion, and clinical
  variables in obese adults
• Examine the effects of intensity of exercise
  training on exercise adherence, GH secretion, and
  clinical variables in obese adults

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Colleagues and Collaborators

• Pre Doctoral Students
• Kimberly Brill
• Denise Lebsack
• Cathy Pritzlaff-Roy
• Rob Schurrer
• Dixie Thompson
• Laurie Wideman
• Chris Womack
• Post Doctoral Fellows
• Jody Clasey
• Jill Kanaley
• Jim Roemmich

• Rob Abbott
• Stacey Anderson
• Cy Bowers
• Claude Bouchard
• JP Despres
• Bill Evans
• Glenn Gaesser
• Margaret Gutgesell
• Mark Hartman
• Jim Patrie
• Alan Rogol
• Michael Thorner
• Johannes Veldhuis

• Research Assistants
• Kirsten Frick
• Dee Dee Watson
• Judy Weltman

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