Effects of Short Term Administration of Recombinant Human Growth Hormone to Elderly People*
We evaluated the effects of recombinant human GH (rhGH) in 16 men and women more than 60 yr of age. After 10 days of dietary equilibration and control collections, subjects were randomly assigned to receive 0.03, 0.06, or 0.12 mg/kg rhGH by daily injection for 7 days. A brisk rise in circulating somatomedin-C (insulin-like growth factor-I) occurred in all subjects, and this rise was dose dependent. rhGH produced striking changes in nitrogen retention, sodium excretion, and the parathyroid-vitamin D axis. Twenty-four-hour urinary nitrogen excretion decreased from 8.00 +/- 0.33 to 5.01 +/- 0.33 g (P less than 0.001), and sodium excretion decreased from 45.9 +/- 2.96 to 21.2 +/- 3.48 mmol/day (P less than 0.001). Serum calcium concentrations did not change, but serum inorganic phosphorus levels of 1.08 +/- 0.04 mmol/L at baseline increased significantly after rhGH treatment to 1.33 +/- 0.04 mmol/L (P less than 0.001). Increases were also observed in circulating PTH (53.2 +/- 6 vs. 39.5 +/- 4.2 ng/L; P less than 0.01) and calcitriol (82.8 vs. 65.8 pmol/L; P less than 0.05). A rise in serum osteocalcin (10.3 +/- .86 vs. 8.0 +/- 0.5 micrograms/L; P less than 0.05) was accompanied by increased urinary excretion of hydroxyproline (628 +/- 63 vs. 406 +/- 44 mumol/day; P less than 0.01). Despite the reduction in sodium excretion, marked increases were observed in urinary calcium (6.04 +/- 0.97 vs. 3.27 +/- 0.40 mmol/day; P less than 0.01). rhGH significantly impaired oral glucose tolerance and reduced insulin sensitivity, but was otherwise well tolerated and produced no systematic changes in weight or blood pressure. The results of this study indicate that rhGH requires further study as a potential agent for attenuating or reversing the loss of muscle and bone in elderly people.
Available from: ncbi.nlm.nih.gov
- "While these initial reports suggested that recombinant GH could be a new anti-aging drug, there are now concerns about whether GH treatment is actually harmful due to potential side effects (Laron 2005). The adverse reactions reported are consistent with those present in humans and animals with high levels of GH, such as hyperinsulinemia and glucose intolerance, arthritis, hypertension, edema, congestive heart failure and possibly increased tumorogenesis (Vance 1990; Marcus et al. 1990; Moon et al. 1950; Cullen et al. 1990). Animal studies looking at GH treatment during aging found improvements in microvascular blood supply and partial reversal of age-related bone marrow loss and thymic regeneration (Sonntag et al. 2000; French et al. 2002). "
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ABSTRACT: The role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in normal brain function is not well understood. Studies looking at cognition in humans with GH deficiency have produced controversial results. Experiments in which GH is administered to rodents have shown an apparent improvement in learning and memory. However, studies in which GH deficient or resistant mice were tested in learning and memory tasks reveal that these animals have normal cognitive performance and that their neural function does not deteriorate with age at the same rate as their normal siblings. Further research into this phenomenon revealed that these animals have elevated GH and IGF-1 expression in the hippocampus compared to normal animals. Additional studies with GH deficient and resistant mice suggested that these mutants experience a delay in age-related decline in locomotor activity and exploratory behavior. Data indicate that GH/IGF-1 deficiency and resistance do not impair neural function and instead may offer some degree of protection that results in delayed cognitive and motor aging.
Available from: William D Fraser
- "Decreased PTH sensitivity or relative increased resistance would be expected to result in increased PTH concentration. However, previous studies, using single time point PTH measurement studies, have reported lower, no different, or higher PTH concentrations in AGHD patients compared to healthy controls   . Since PTH shows significant day–night variability, it is possible that the variability in these results may be due to the time of day the measurements were performed. "
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ABSTRACT: Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0.75) was observed when PTH was lagged by 1.5 h in healthy individuals, suggesting that changes in phosphate precede changes in PTH concentration. PTH/CT(x) and PTH/PINP showed maximum correlation when CT(x) (r = 0.68) and PINP (r = 0.71) were lagged by 3 h. In AGHD patients, compared to controls the maximum correlation between PTH/phosphate (r = 0.88, P = 0.007), PTH/CTx (r = 0.61, P = 0.027), and PTH/PINP (r = 0.65, P = 0.028) was observed when the lag time was reduced by 1.5 h in all variables, with changes in PTH and phosphate occurring at concurrent time points. Our data suggest decreased end-organ sensitivity to the effects of PTH in AGHD patients, resulting in a significantly lower NcAMP, low bone turnover, and higher calcium excretion in the presence of significantly higher PTH concentrations. We have also demonstrated that changes in serum phosphate precede those of PTH, which in turn precede changes in bone resorption and formation in healthy individuals. This relationship was altered in AGHD patients. These results suggest a possible role for GH in regulating PTH secretion and the bone remodeling process.
Available from: dspace.hil.unb.ca
- "appon et al . ( 1994 ) , dem onstrate that IGF - I concentrations can function independently o f the changes in acute growth hormone concentrations . Other investigators have suggested that the magnitude o f resting IGF - I may play an important role in the responsiveness to an exercise - induced growth hormone increase ( Marcus et al . , 1990 ) . Marcus et al . ( 1990 ) observed a blunted response o f IGF - I on the last day o f exogenous growth hormone administration , indicating the possibility o f an upper limit o f responsiveness . If an upper limit does exist , this would help explain the lack o f IGF - I response found by Kraemer et al . ( 1995b ) . Subjects used in the study by Kraemer et al ."
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