Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men

1991 ◽  
Vol 124 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Hiroshi Bando ◽  
Chenyu Zhang ◽  
Yukinobu Takada ◽  
Ryuichi Yamasaki ◽  
Shiro Saito

Abstract. The GHRH test and L-dopa test were performed in 12 normal young men (24.1 ± 1.1 years) and 12 normal elderly men (77.8±1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0± 11.7 vs 86.7± 11.6 μg/1). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 ±5.9 vs 11.2 ± 2.1 μg · h−1 · 1−1, p<0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa test in young and elderly men were 32.0±2.7 vs 20.3±1.8 ng · h−1 · 1−1 (p<0.001), and 21.8±4.6 vs 5.4±1.1 μg · h−1 · 1 (p<0.01), respectively, indicating decreased releases of GHRH and GH in the elderly. Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the elderly group. The elderly group showed a significant correlation between the basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests. These results suggest that elderly men have a decreased reserve of hypothalamic GHRH, resulting in secondarily impaired GH release, which may lead to a lower level of IGF-I than in young men.

1990 ◽  
Vol 122 (6) ◽  
pp. 745-752 ◽  
Author(s):  
Patrick Pagesy ◽  
Jacques Y. Li ◽  
Françoise Rentier-Delrue ◽  
Olivier Delalande ◽  
Yves Le Bouc ◽  
...  

Abstract. Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level < 4 μg/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 ± 16.1 μg/l, mean ± sem). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1± 0.37 vs 51.5± 34.1 μg · (10−6 cells) · min−1, p< 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6. In conclusion, because of the variability of the biosynthetic and secretory potential of the somatotropic adenomas, patients harbouring this type of pituitary tumours can exhibit a wide range of plasma GH levels. In acromegaly with minimal elevation of plasma GH, the synthesis of SRIH by the adenoma cells themselves could play a role in the inhibition of GH expression.


1997 ◽  
Vol 272 (1) ◽  
pp. E139-E146 ◽  
Author(s):  
A. A. Portale ◽  
E. T. Lonergan ◽  
D. M. Tanney ◽  
B. P. Halloran

We examined the effect of aging on the relationship between the concentrations of blood ionized calcium and of serum parathyroid hormone (PTH) in 22 healthy men [9 elderly (age 74 +/- 2 yr) and 13 young (age 39 +/- 1 yr)] in whom the glomerular filtration rate was > 70 ml/min. Throughout a 24-h period, serum concentrations of PTH in the elderly men were twice those in the young men, whereas blood ionized calcium did not differ between the two groups. With intravenous infusion of calcium gluconate, the minimum PTH concentration was two- to threefold higher in the elderly men. With infusion of NaEDTA. the maximum PTH concentration was 20% higher in the elderly men. The calcium set point for PTH release was higher in the elderly than in the young men (4.71 +/- 0.04 vs. 4.54 +/- 0.03 mg/dl, respectively, P < 0.005). In these healthy men, the age-related increase in serum PTH could not be attributed to a sustained decrease in concentration of either blood ionized calcium or 1,25-hydroxyvitamin D. These findings suggest that, with aging, the relationship between calcium and PTH is altered such that at any given level of calcium, the concentration of PTH is higher.


2005 ◽  
Vol 152 (4) ◽  
pp. 575-580 ◽  
Author(s):  
Sander V Haijma ◽  
P Sytze van Dam ◽  
Wouter R de Vries ◽  
Inge Maitimu-Smeele ◽  
Carlos Dieguez ◽  
...  

Objective and design: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0 μg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men. Methods: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m2), nine obese men (mean age 47 years; mean BMI 40.6 kg/m2) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m2). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 μg) and GHRP-6 (93 μg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours. Results: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4 μg/l, P = 0.001; AUC 707 vs 3250 μg/l × 120 min; P = 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 μg/l; AUC 2274 μg/l × 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 μg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P = 0.001). Baseline GH or IGF-I did not differ significantly between groups. Conclusions: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0 μg/l after GHRH + GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.


1992 ◽  
Vol 126 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Geoffrey R Ambler ◽  
Bernhard H Breier ◽  
Andrzej Surus ◽  
Hugh T Blair ◽  
Stuart N McCutcheon ◽  
...  

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p<0.001) and [125I]bGH binding to hepatic membranes (p<0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p<0.05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r=0.82, p<0.001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p<0.001) and [125]bGH membrane binding capacity (r = 0.91, p< 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.


1991 ◽  
Vol 260 (4) ◽  
pp. E651-E661 ◽  
Author(s):  
A. van Coevorden ◽  
J. Mockel ◽  
E. Laurent ◽  
M. Kerkhofs ◽  
M. L'Hermite-Baleriaux ◽  
...  

To delineate the physiological effects of aging on basal levels and temporal patterns of neuroendocrine secretions, the 24-h profiles of cortisol, thyroid-stimulating hormone (TSH), melatonin, prolactin, and growth hormone (GH) levels were simultaneously obtained at frequent intervals in eight healthy, active elderly men, age 67-84 yr and in eight young male adults, age 20-27 yr. The study was preceded by an extended period of habituation to laboratory conditions, and sleep was polygraphically recorded. Mean cortisol levels in the elderly were normal, but the amplitude of the circadian rhythm was reduced. Circulating levels of daytime and nighttime levels of both TSH and GH were greatly diminished in old age. In contrast, prolactin and melatonin concentrations were decreased during the nighttime only. The circadian rises of cortisol, TSH, and melatonin occurred 1-1.5 h earlier in elderly subjects, and the distribution of rapid-eye-movement stages during sleep was similarly advanced, suggesting that circadian timekeeping is modified during normal senescence. Despite perturbations of sleep, sleep-related release of GH and prolactin occurred in all elderly men. Age-related decreases in hormonal levels were associated with a decrease in the amplitude, but not the frequency, of secretory pulses. These findings demonstrate that the normal process of aging involves alterations in the central mechanisms controlling the temporal organization of endocrine release in addition to a reduction of secretory outputs.


1995 ◽  
Vol 268 (4) ◽  
pp. F613-F625
Author(s):  
N. K. Fukagawa ◽  
L. G. Bandini ◽  
M. A. Lee ◽  
J. B. Young

Renal excretory responses to protein feeding were compared in nine young (20-26 yr) and nine elderly (70-89 yr) men. Although protein increased excretion of dopamine and serotonin (5-HT, P < 0.001 for both), the basal excretion of dopamine and 5-HT was less in old than young men (P < 0.05). Protein increased sodium and water excretion in the young; responses in elderly for both were less (P < 0.025). Carbidopa markedly suppressed dopamine and 5-HT excretion in both young and old men. Carbidopa also attenuated protein-induced natriuresis and diuresis and raised serum aldosterone levels in the young but not in the old men. These age-related differences in dopamine and 5-HT excretion were not abolished by alterations in dietary NaCl. Thus, although dopamine excretion is decreased overall in elderly men, sodium and water excretion and aldosterone secretion in the old men were unaffected by alterations in dopamine production. These data suggest that impaired protein-induced natriuresis in the old men may be due to limitations in renovascular responses and that, in young men, dopamine and 5-HT may contribute to the protein-induced changes in renovascular function.


1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90


1999 ◽  
Vol 27 (02) ◽  
pp. 167-176 ◽  
Author(s):  
Myeong Soo Lee ◽  
Chang Won Kang ◽  
Hoon Ryu ◽  
Jong-Duak Kim ◽  
Hun-Taeg Chung

We observed the response of plasma growth hormone(GH), insulin-like growth factor-I(IGF-I) and testosterone(T) to an acute period of ChunDoSunBup(CDSB) Qi-training. Although the basal level of GH was not different between the two groups, after the portion of the training in which the subjects were physically active (the mid-training point), plasma GH levels increased by 7.26 fold (p < 0.05) in the elderly trainees and by 1.66 fold (p < 0.05) in the young. In response to CDSB Qi-training, IGF-I levels in the young increased significantly at mid-training point, but there were no increase in the elderly. Significant correlations existed between GH and IGF-I levels in the young subjects, but not in the elderly. The T level at the mid-training point increased significantly in elderly subjects but not in the young. These results suggest that CDSB Qi-training is a potential method for modulating of the secretion of growth factor in the young and the elderly, but that the elderly IGF-I response does not equal that of the young. In addition, our study suggests CDSB Qi-training may be one mode of therapy applicable to growth factor related disorders such as GH deficiency in children and osteoporosis in the elderly, especially women.


1995 ◽  
Vol 75 (1) ◽  
pp. 57-61 ◽  
Author(s):  
C. Farmer ◽  
H. Lapierre

Pituitaries from female Yorkshire pig fetuses (90 d, n = 26; 110 d, n = 17) and 6-mo-old pigs (n = 5) were enzymatically dispersed, plated, and cultured for 47 h. The cells were then rinsed and incubated for 22 h with testing media containing 0, 50, 100, 200, 300 or 400 ng mL−1 of IGF-I. Half of the wells from each concentration of IGF-I were then incubated for an additional 3 h with concentrations of IGF-I similar to those in the previous incubation, while the other half also had GRF added to the testing media to reach a final concentration of 10−8 M. Culture media were then collected from all the wells, were frozen, and later assayed for GH. Irrespective of whether GRF was present, IGF-I decreased pituitary secretion of GH (P < 0.001). A significant negative response to IGF-I was already present at the dose of 50 ng mL−1 (P < 0.0001). However, the extent of the GH response to IGF-I seen in pigs of various ages differed depending on whether GRF was present. The present results therefore establish that IGF-I does exert a negative feedback on pituitary GH secretion in swine and that the age-related changes in this feedback are dependent on the presence of GRF. In swine, it appears that high circulating concentrations of GH in late-gestation fetuses are not a result of a lesser sensitivity of the somatotroph to the inhibitory actions of IGF-I. Key words: Pig, cell culture, pituitary, IGF-I, growth hormone, age


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