Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men.

Mean plasma GH concentrations are controlled by the frequency, amplitude, and duration of underlying GH secretory bursts as well as by the half-life of endogenous GH. We investigated the specific mechanisms that subserve the clinically recognized negative effects of age and adiposity on mean serum GH concentrations. To this end, 21 healthy men, aged 21-71 yr, who were of nearly normal body weight underwent blood sampling at 10-min intervals for 24 h. Deconvolution analysis was used to estimate specific features of GH secretion and clearance. Compared to younger men, the older tertile of men had significant reductions in 1) GH secretory burst frequency, 2) the half-life of endogenous GH, and 3) the daily GH secretory rate, but not 4) GH secretory burst half-duration, amplitude, or mass. Linear regression analysis disclosed that age was a major negative statistical determinant of GH secretory burst frequency (r = -0.80; P = 0.005) and endogenous GH half-life (r = -0.70; P = 0.024). Body mass index, an indicator of relative obesity, was a significant negative correlate of GH half-life (P = 0.045) and GH secretory burst amplitude (P = 0.031). Age and body mass index each correlated negatively with the daily GH secretion rate (P = 0.0031 and P = 0.027, respectively), and together accounted for more than 60% of the variability in 24-h GH production rates (r = -0.78; P = 0.00056). On the average, for a normal body mass index, each decade of increasing age attenuated the GH production rate by 14% and the GH half-life by 6%. Conversely, each unit increase in body mass index, at a given age, reduced the daily GH secretion rate by 6%. We conclude that age and relative adiposity are distinct and specific correlates of individual attributes of GH secretion and clearance in men.

[1]  B. Hansen,et al.  Metabolic clearance rates of synthetic human growth hormone in lean and obese male rhesus monkeys. , 1988, The Journal of clinical endocrinology and metabolism.

[2]  F. Cordido,et al.  Cholinergic receptor activation by pyridostigmine restores growth hormone (GH) responsiveness to GH-releasing hormone administration in obese subjects: evidence for hypothalamic somatostatinergic participation in the blunted GH release of obesity. , 1989, The Journal of clinical endocrinology and metabolism.

[3]  J. Meites,et al.  Growth hormone restores protein synthesis in skeletal muscle of old male rats. , 1985, Journal of gerontology.

[4]  M. Vance,et al.  Half-time of endogenous growth hormone (GH) disappearance in normal man after stimulation of GH secretion by GH-releasing hormone and suppression with somatostatin. , 1989, The Journal of clinical endocrinology and metabolism.

[5]  Ž. Reiner,et al.  Effect of l-dopa on growth hormone, glucose, insulin, and cortisol response in obese subjects. , 2009, Experimental and clinical endocrinology.

[6]  A. Rogol,et al.  Impact of intensive venous sampling on characterization of pulsatile GH release. , 1987, The American journal of physiology.

[7]  E. Arvat,et al.  Growth hormone (GH) responsiveness to combined administration of arginine and GH-releasing hormone does not vary with age in man. , 1990, The Journal of clinical endocrinology and metabolism.

[8]  H. Roffwarg,et al.  Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. , 1972, The Journal of clinical endocrinology and metabolism.

[9]  N. Ling,et al.  Age-related changes in plasma growth hormone response to growth hormone-releasing factor in man. , 1984, The Journal of clinical endocrinology and metabolism.

[10]  P. Björntorp,et al.  Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. , 1984, British medical journal.

[11]  A. Rogol,et al.  Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. , 1987, The Journal of clinical endocrinology and metabolism.

[12]  K. Alberti,et al.  Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. , 1988, The Journal of clinical investigation.

[13]  J D Veldhuis,et al.  Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: relationship to age, pubertal status, and body mass. , 1992, The Journal of clinical endocrinology and metabolism.

[14]  L. Frohman,et al.  Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. , 1984, The New England journal of medicine.

[15]  M L Johnson,et al.  Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. , 1991, The Journal of clinical endocrinology and metabolism.

[16]  J. Epelbaum,et al.  Antiserum to somatostatin reverses starvation-induced inhibition of growth hormone but not insulin secretion. , 1978, Endocrinology.

[17]  P. Plotsky,et al.  Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat. , 1985, Science.

[18]  N. Mauras,et al.  Increased hGH Production Rate after Low-Dose Estrogen Therapy in Prepubertal Girls with Turner's Syndrome , 1990, Pediatric Research.

[19]  M. Shaw,et al.  Basal plasma growth hormone levels in man: new evidence for rhythmicity of growth hormone secretion. , 1990, The Journal of clinical endocrinology and metabolism.

[20]  P. Sönksen,et al.  The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. , 1989, The New England journal of medicine.

[21]  Z. Laron,et al.  Plasma Growth Hormone Response to Oral Clonidine as Compared to Insulin Hypoglycemia in Obese Children and Adolescents , 1984, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[22]  A. Iranmanesh,et al.  Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus. , 1989, The Journal of clinical endocrinology and metabolism.

[23]  N. Skakkebaek,et al.  BENEFICIAL EFFECTS OF GROWTH HORMONE TREATMENT IN GH-DEFICIENT ADULTS , 1989, The Lancet.

[24]  J. Beyer,et al.  Naloxone increases the response of growth hormone and prolactin to stimuli in obese humans , 1987, Journal of endocrinological investigation.

[25]  L. Sjöström,et al.  Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. , 1983, The Journal of clinical investigation.

[26]  D. Rudman,et al.  Effects of human growth hormone in men over 60 years old. , 1990, The New England journal of medicine.

[27]  D. Styne,et al.  Changes in basal and stimulated growth hormone secretion in the aging rhesus monkey: a comparison of chair restraint and tether and vest sampling. , 1990, The Journal of clinical endocrinology and metabolism.

[28]  A. Schally,et al.  Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. , 1987, The Journal of clinical endocrinology and metabolism.

[29]  A. Tofani,et al.  Differential effects of feeding on the ultradian variation of the growth hormone (GH) response to GH-releasing hormone in normal subjects and patients with obesity and anorexia nervosa. , 1988, The Journal of clinical endocrinology and metabolism.

[30]  W. Steffee,et al.  Total human body protein synthesis in relation to protein requirements at various ages , 1975, Nature.

[31]  M. Vitiello,et al.  Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. , 1985, Journal of gerontology.

[32]  H. E. Palmer,et al.  Effect of age on growth hormone secretion in man. , 1973, The Journal of clinical endocrinology and metabolism.

[33]  N. Mauras,et al.  Augmentation of growth hormone secretion during puberty: evidence for a pulse amplitude-modulated phenomenon. , 1987, The Journal of clinical endocrinology and metabolism.

[34]  M. Shaw,et al.  A rapid and simple assay for growth hormone-binding protein activity in human plasma. , 1988, Acta endocrinologica.

[35]  R. Manna,et al.  Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects. , 1987, Hormone research.

[36]  P. Gorden,et al.  Abscence of sleep-related growth hormone peaks in aged normal subjects and in acromegaly. , 1972, The Journal of clinical endocrinology and metabolism.

[37]  S. Melmed,et al.  Effects of Insulin on Rat Anterior Pituitary Cells: Inhibition of Growth Hormone Secretion and mRNA Levels , 1986, Diabetes.

[38]  D. Cook,et al.  THE RESPONSE OF OBESE SUBJECTS TO CONTINUOUS INFUSION OF HUMAN PANCREATIC GROWTH HORMONE‐RELEASING FACTOR 1–44 , 1985, Clinical endocrinology.

[39]  A C Herington,et al.  Identification and characterization of specific binding proteins for growth hormone in normal human sera. , 1986, The Journal of clinical investigation.

[40]  A. Frantz,et al.  Effects of Estrogen and Sex Difference on Secretion of Human Growth Hormone1 , 1965 .

[41]  S. Margolis,et al.  Integrated concentrations of growth hormone, insulin, C-peptide and prolactin in human obesity. , 1982, Metabolism: clinical and experimental.

[42]  R. Urban,et al.  Biophysical modeling of sensitivity and positive accuracy of detecting episodic endocrine signals. , 1989, The American journal of physiology.

[43]  R. Marcus,et al.  Effects of short term administration of recombinant human growth hormone to elderly people. , 1990, The Journal of clinical endocrinology and metabolism.

[44]  M L Johnson,et al.  The pituitary gland secretes in bursts: appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[45]  L. Agnati,et al.  Reduced growth hormone releasing factor (GHRF)-like immunoreactivity and GHRF gene expression in the hypothalamus of aged rats , 1989, Peptides.

[46]  K. Spik,et al.  Increased pituitary response to somatostatin in aging male rats: relationship to somatostatin receptor number and affinity. , 1989, Neuroendocrinology.

[47]  R. McCARTER,et al.  The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. , 1985, The Journal of clinical endocrinology and metabolism.

[48]  M. Kutner,et al.  Impaired growth hormone secretion in the adult population: relation to age and adiposity. , 1981, The Journal of clinical investigation.