Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging

1990 ◽  
Vol 123 (2) ◽  
pp. 169-173 ◽  
Author(s):  
E. Ghigo ◽  
S. Goffi ◽  
E. Arvat ◽  
M. Nicolosi ◽  
M. Procopio ◽  
...  

Abstract. In 11 elderly normal subjects and in 17 young healthy subjects we studied the response of plasma growth hormone to GH-releasing hormone (GHRH(29), 1 μg/kg iv) alone and preceded by pyridostigmine ( 120 mg orally 60 min before GHRH), a cholinesterase inhibitor likely able to suppress somatostatin release. The GH response to pyridostigmine alone was also examined. Basal plasma GH levels were similar in elderly and young subjects. In the elderly, GHRH induced a GH rise (AUC, median and range: 207.5, 43.5-444.0 μg · 1−1 · h−1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5-2313.5 μg · 1−1 · h−1). The pyridostigmine-induced GH rise in the elderly was similar to that in young subjects (300.5, 163.0-470.0 vs 265.0, 33.0-514.5 μg · 1−1 · h−1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 μg · 1−1 · h−1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 μg · 1−1 · h−1; p = 0.0001 vs GHRH alone). However, the GH response to pyridostigmine + GHRH was significantly lower (p = 0.0001) in elderly than in young subjects. In conclusion, the cholinergic enhancement by pyridostigmine is able to potentiate the blunted GH response to GHRH in elderly subjects, inducing a GH increase similar to that observed after GHRH alone in young adults. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in normal aging. However, a decreased GH response to combined administration of pyridostigmine and GHRH in elderly subjects suggests that other abnormalities may coexist, leading to the secretory hypoactivity of somatotropes.

1993 ◽  
Vol 138 (2) ◽  
pp. 211-218 ◽  
Author(s):  
J. Muruais ◽  
A. Peñalva ◽  
C. Dieguez ◽  
F. F. Casanueva

ABSTRACT His-d-Trp-Ala-Trp-d-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and α-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed. In adult Beagle dogs (n = 10), GHRP-6 (90 μg i.v.) increased basal GH levels from 2·6 ± 1·5 to 14·4 ± 3·1 μg/l (mean ± s.e.m.) after 15 min. GHRH (50 μg i.v.) induced a GH peak of 9·7 ± 2·2 μg/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 ± 9·0 μg/l (P <0·01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37·9 ± 10·1 μg/l P <0·05), while the muscarinic blocker atropine (100 μg i.v.) completely abolished (GH peak lower than 2 μg/l) the stimulatory action of GHRP-6. On the other hand, administration of the α-2 adrenergic agonist clonidine (4 pg/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6. Finally, while the α-1 adrenergic agonist methoxamine (5 mg i.v.) did not significantly increase GH responses to GHRP-6, administration of the α-1 adrenoceptor antagonist prazosin (20 mg i.v.) reduced GHRP-6-induced GH secretion (area under curve, 206 ± 39 vs 557 ± 172, P <0·05). In summary, the synergistic effect of the combined administration of maximal doses of GHRP-6 and GHRH suggests that these two peptides act through different mechanisms. The finding that cholinergic drugs were able to modulate the GH secretion elicited by GHRP-6 argues against the hypothesis that such a peptide acts by influencing hypothalamic somatostatin release and suggests that it acts directly at the pituitary level. Finally, the unexpected lack of effect of clonidine and the inhibitory effect of prazosin on GHRP-6-induced GH secretion suggests that the role of α-adrenergic pathways in GH secretion is more complex than previously thought. Journal of Endocrinology (1993) 138, 211–218


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2235
Author(s):  
Alyann Otrante ◽  
Amal Trigui ◽  
Roua Walha ◽  
Hicham Berrougui ◽  
Tamas Fulop ◽  
...  

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = −0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (β = 0.28, p < 0.002, and β = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 926.1-926
Author(s):  
M. Mrabet ◽  
S. Boussaid ◽  
S. Jemmali ◽  
H. Sahli ◽  
H. Ajlani ◽  
...  

Background:Tuberculosis is still endemic all over the world. The incidence of tuberculous spondylodiscitis (TS) is steadily increasing. Clinical features and outcomes of this affection are various and depending on various parameters, including age.Objectives:Our objective was to explore the differences in presentation and the results of further investigations and the prognosis of TS between young and elderly subjects.Methods:We conduct a retrospective and descriptive study in a single rheumatology department. Data were collected from files of patients hospitalized in the past 20 years (2000-2020) who have been diagnosed with TS. We carried out a comparative study concerning the clinical biological, imaging features and outcomes between young subjects and subjects aged over 65 years.Results:Fifty-two cases of TS were collected (37F/15M). The mean age of the population was 55.21 years ± 17.79 [19-91]. Thirty-three patients (69.2%) were classified as young versus 16 elderly patients (30.8%), with female predominance in both groups (69.4% and 75% respectively, p = 0.57). Young subjects was more frequently vaccinated (88.9%) by Bacillus Calmette–Guérin (BCG) (p < 0.001). A delayed diagnosis was noted in both groups (p = 0.24). Lumbar spine involvement was the most common (57.7%). In the two age ranges, the onset of the disease was progressive (p = 0.22), characterized by segmental spine stiffness (p = 0.57) and lumbar pain with general signs (p = 0.27), such as: impaired general condition, fever, night sweats and weight loss. Biological inflammatory syndrome and normochrome normocytic anemia were encountered in both cases (p = 0.08 and p = 0.2, respectively). Standard X-rays and Computed tomography were more performed in young subjects (94.4% and 69.4%, respectively; p < 0.001), unlike magnetic resonance imaging which was more common in elderly subjects but with no statistically significant difference (p = 0.22). Disc pinch, erosion of vertebral plateaus and vertebral collapse were the major signs (82.7%, 65.4% and 67.3%, respectively). Clinical, biological and imaging arguments contributed to positive diagnosis in both groups (p = 0.24). Common medical treatment was anti-tuberculosis: Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E) and physical treatment such as immobilization witch was more common in the eldery (56.3%, p = 0.16). The evolution of the disease was characterized by a clear improvement of young subjects during the second week of treatment (p < 0.001). A more frequent clinical improvement in older subjects was during the fourth week but with no statistically significant difference (p = 0.13). The occurrence of immediate complications was more frequent in the elderly (p = 0.23) with a predominance for drug complications (56.3%) such as: hepatic cytolysis (12.5%), hyperuricemia (18.8%) and major intolerance to anti-tuberculosis (18.8%).Conclusion:TS is a frequent condition that needs to be treated rapidly. the clinical presentation of TS in the elderly is less noisy which leads to more frequent complications and mortality.Disclosure of Interests:None declared


1983 ◽  
Vol 65 (2) ◽  
pp. 155-157 ◽  
Author(s):  
T. G. Cotter ◽  
K. O'Malley

1. Neutrophils from drug-free elderly subjects produced approximately 50% less cyclic AMP in response to isoprenaline than did neutrophils from young subjects. A significant difference in basal cyclic AMP levels was also evident (elderly 2.8 ± 0.37; young 4.9 ± 0.36 pmol of cAMP/107 cells; P < 0.05). 2. With a range of anti-neutrophil monoclonal antibodies no evidence of age-related neutrophil population heterogeneity was found. 3. These findings indicate that the age-related decline in β-adrenoceptor responsiveness is not due to changes in the neutrophil population. 4. The present results support the hypothesis that there is a generalized decline in β-adrenoceptor-mediated responsiveness in the elderly.


1994 ◽  
Vol 86 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Penelope J. Neild ◽  
Denise Syndercombe-Court ◽  
W. R. Keatinge ◽  
G. C. Donaldson ◽  
M. Mattock ◽  
...  

1. Six elderly (66-71 years) and six young (20-23 years) subjects (half of each group women) were cooled for 2 h in moving air at 18°C to investigate possible causes of increased mortality from arterial thrombosis among elderly people in cold weather. Compared with thermoneutral control experiments, skin temperature (trunk) fell from 35.5 to 29.5°C, with little change in core temperature. 2. Erythrocyte count rose in the cold from 4.29 to 4.69 × 1012/l, without a change in mean corpuscular volume, indicating a 14% or 438 ml decline in plasma volume; increased excretion of water, Na+ and K+ accounted for loss of only 179 ml of extracellular water. 3. Plasma cholesterol and fibrinogen concentrations rose in the elderly subjects from 4.9 mmol/l and 2.97 g/l (control) to 5.45 mmol/l and 3.39 g/l in the cold, and in the young subjects from 3.33 mmol/l and 1.84 g/l (control) to 3.77 mmol/l and 2.07 g/l in the cold. Increases were significant for the elderly subjects, the young subjects and the group as a whole, except for cholesterol in the young subjects, and all were close to those expected from the fall in plasma volume. 4. Plasma levels of Protein C and factor X did not increase significantly in the cold in the elderly subjects, young subjects, or the group as a whole. 5. The results suggest that loss of plasma fluid in the cold concentrates major risk factors for arterial thrombosis, while small molecules, including protective Protein C, redistribute to interstitial fluid.


1999 ◽  
Vol 9 (3) ◽  
pp. 197-205
Author(s):  
L.L. Borger ◽  
S.L. Whitney ◽  
M.S. Redfern ◽  
J.M. Furman

Postural sway during stance has been found to be sensitive to moving visual scenes in young adults, children, and those with vestibular disease. The effect of visual environments on balance in elderly individuals is relatively unknown. The purpose of this study was to compare postural sway responses of healthy elderly to those of young subjects when both groups were exposed to a moving visual scene. Peak to peak, root mean squared, and mean velocity of the center of pressure were analyzed under conditions combining four moving scene amplitudes ( 2 . 5 ∘ , 5 ∘ , 7 . 5 ∘ , 10 ∘ ) and two frequencies of scene movement (0.1 Hz, 0.25 Hz). Each visual condition was tested with a fixed floor and sway referenced platform. Results showed that elderly subjects swayed more than younger subjects when experiencing a moving visual scene under all conditions. The elderly were affected more than the young by sway referencing the platform. The differences between the two age groups were greater at increased amplitudes of scene movement. These results suggest that elderly are more influenced by dynamic visual information for balance than the young, particularly when cues from the ankles are altered.


1996 ◽  
Vol 134 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Kunihiko Hanew ◽  
Aki Tanaka ◽  
Atsushi Utsumi ◽  
Akira Sugawara ◽  
Keishi Abe

Hanew K, Tanaka A, Utsumi A, Sugawara A, Abe K, Plasma GH responses to human GHRH-antagonist in normal subjects. Eur J Endocrinol 1996;134:67–72. ISSN 0804–4643 The effect of GHRH-antagonist {N-Ac-Tyr1, d-Arg2) GRF-(1–29)-NH2} on plasma GH morning and evening secretion was evaluated in 14 normal subjects (10 males, 4 females, aged 19–25 years). Plasma GH was determined using a high sensitivity IRMA kit (detection limit, 0.006 μg/l). After intravenous infusion of GHRH-antagonist (100 μg/100 ml saline over 75 min) in the morning, plasma GH remained constant during the 150 min post-infusion (N = 6). In contrast, when GHRH-antagonist was administered in the evening, plasma GH showed a clear and gradual decrease through the initial 90 min and returned to baseline levels at 150 min. Plasma GH values were also significantly lower from 75 min to 135 min when compared to physiological fluctuations in plasma GH (P < 0.05). Other anterior pituitary hormones remained unaffected by GHRH-antagonist. In conclusion, our data suggest that evening basal GH secretion, but not morning GH secretion, is maintained by endogenous GHRH. K Hanew, The Second Department of Internal Medicine, Tohoku University School of Medicine. 1-1 Seiryocho, Sendai 980, Japan


2021 ◽  
pp. 19-21
Author(s):  
Nutan Bala ◽  
Priyanka Priyanka ◽  
Sheela Kumari ◽  
Debarshi Jana

The effect of age on the peripheral nervous system was investigated by clinical examination and neurophysiological studies in 59 subjects aged 60- 103 years and 23 young subjects. Afull laboratory screen for factors which, though clinically silent, may constitute risk factors (RFs) for peripheral neuropathy was also performed in the elderly subjects. Our ndings show that the presence of RFs affects exceptionally the electrophysiological parameters in a statistically signicant way. The age-dependent changes in nerve conduction parameters were well predicted by non-linear models. The simultaneous electromyographical study demonstrates the re-innervation capacity of the motor system


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.


2002 ◽  
Vol 174 (3) ◽  
pp. 387-394 ◽  
Author(s):  
AE Rigamonti ◽  
SM Bonomo ◽  
SG Cella ◽  
EE Muller

GH-releasing peptides (GHRPs), a class of small synthetic peptide and non-peptide compounds, act on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in both humans and other animals. GHRPs, like corticotropin-releasing hormone (CRH), also possess acute ACTH- and cortisol-releasing activity, although the mechanisms underlying the stimulatory effect of GHRPs on the hypothalamo-pituitary-adrenal (HPA) axis are still unclear. In recent years, studies in humans and other animals have provided evidence that the rebound GH rise which follows withdrawal of an infusion of somatostatin (SS) (SSIW) is due, at least in part, to the functional activation of GH-releasing hormone (GHRH) neurons of the recipient organism. Unexpectedly, in humans, SS infusion, at a dose inhibiting basal GH secretion, has been associated with an activation of the HPA axis, leading to the hypothesis that this response was mediated, at least in part, by a central nervous system ACTH-releasing mechanism activated by the SS-induced decrease in GH secretion. Interestingly, the rebound GH rise which follows SSIW was magnified by the administration, before SS withdrawal, of a GHRP, implying that the SSIW approach could also be exploited to investigate in vivo the functional interaction in the process of GH and/or ACTH/cortisol secretion between endogenous GHRH (and/or other ACTH-releasing mechanisms) and GHRPs. In the present study, six young beagle dogs were given, on different occasions, at the beginning and at the end of a 3-h i.v. infusion of SS or saline (SAL), a bolus of physiological SAL or a GHRP compound, EP51216. SSIW induced a GH rebound rise without affecting plasma cortisol concentrations, while the withdrawal of SAL infusion was ineffective on either hormone paradigm. Administration of EP51216 at the beginning of SAL infusion evoked release of both GH and cortisol, whereas EP51216 administration at the withdrawal of SAL infusion evoked somatotroph and cortisol responses which were reduced in amplitude and duration. SS infusion significantly reduced the secretion of GH elicited by EP51216 but did not affect the rise of plasma cortisol levels. Interestingly, SSIW resulted in a marked enhancement of the somatotroph and cortisol responses evoked by EP51216. The marked rise of plasma GH levels induced by the GHRP after SSIW recalled that occurring after acute combined administration of recombinant human GHRH and EP51216, implying that exogenously delivered GHRP had synergized with the endogenous GHRH release triggered by SSIW. In contrast, acute combined administration of GHRH and the GHRP induced a cortisol response not different from that induced by GHRP alone, indicating that endogenous GHRH release was not involved in the enhanced cortisol response following EP51216 administration after SSIW. Similarly, the direct involvement of endogenous CRH could be ruled out, since i.v. administration of ovine CRH after SSIW evoked cortisol peak levels not different from those evoked by CRH at the withdrawal of SAL infusion. In conclusion, enhancement of the GH response to EP51216 alone by SSIW, to an extent reminiscent of that following combined administration of GHRH and EP61216, reinforces the view that SSIW elicits release of endogenous GHRH. Further studies are indeed necessary for a better understanding of the mechanisms underlying the enhanced cortisol response, since from now on the involvement of endogenous GHRH or CRH can be ruled out.


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