Article Sidebar
Article Details
Copyright remains in the Author’s name. The work is licensed under a Creative Commons Attribution - Noncommercial Works License. Authors are required to complete and sign an Author Agreement form that outlines Author and Publisher rights and terms of publication. The Agreement form should be uploaded along with other submissions files and any submission will be considered incomplete without it [forthcoming].
Material submitted for publication in the SAMJ is accepted provided it has not been published or submitted for publication elsewhere. Please inform the editorial team if the main findings of your paper have been presented at a conference and published in abstract form, to avoid copyright infringement. The SAMJ does not hold itself responsible for statements made by the authors.
Previously published images
If an image/figure has been previously published, permission to reproduce or alter it must be obtained by the authors from the original publisher and the figure legend must give full credit to the original source. This credit should be accompanied by a letter indicating that permission to reproduce the image has been granted to the author/s. This letter should be uploaded as a supplementary file during submission.
Main Article Content
Contribution of growth hormone-releasing hormone and somatostatin to decreased growth hormone secretion in elderly men
Abstract
Objective. The pathophysiology of the decline in circulating growth hormone (GH) concentrations that may occur with ageing remains elusive. We have investigated the potential contributions of decreased endogenous GH-releasing hormone (GHRH) and increased somatostatin secretion to this phenomenon.
Design and methods. The strategy used was to stimulate GH secretion in 8 young (20 - 24 years old, body mass index (BMI) 22.8 ± 2.8 kg/m2 ) and 8 elderly (68 - 82 years old, BMI 23.4 ± 1.6 kg/m2 ) male subjects on separate occasions by means of: (i) intravenous bolus 0.5 pg/kg D-Ala2 GHRH(1-29)-NR alone; (ii) 0.5 pg/kg GHRH after pretreatment with two oral doses of 50 mg atenolol (to inhibit somatostatin secretion); (iii) 1.25 mg oral bromocriptine alone (to increase endogenous GHRH and/or inhibit somatostatin); (iv) 50 mg oral atenolol plus 1.25 mg oral bromocriptine; and (v) 0.5 Jlg/kg GHRH after pre-treatment with 1.25 mg oral bromocriptine.
Results. The elderly men had a significantly lower peak and area under curve (ADC) GH response to intravenous GHRH when compared with 8 yoU?g men (peak 3.1 ± 1.0 ng/ml v. 21.6 ± 5.0 ng/ml, ADC 205 ± 56 ng/ml/min v. 1 315 ± 295 ng/ml/min, P < 0.05). Pre-treatment with atenolol before GHRH administration produced no significant increase in peak and AUC GH response in both groups, which remained lower in the elderly men than in their young counterparts (peak 5.5 ±·1.8 ng/ml v. 29.3 ± 7.0 ng/ml, ADC 327 ± 90 ng/ml/min v. 2 017 ± 590 ng/ml/min, P < 0.05). Bromocriptine alone did not cause a significant rise in CH concentration in either elderly or young subjects (peak 3.1 ± 1.1 v. 8.8 ± 3.2 ng/ml, P > 0.05). When atenolol was administered before bromocriptine, both groups responded but the elderly subjects had a significantly greater peak and ADC response (peak 3.6 ± 0.7 v. 10:7 ± 2.1 ng/ml; ADC 191 ± 39 v. 533 ± 125 ng/mllmin, P < 0.05). Bromocriptine given before CHRH failed to potentiate CHRH action on CH release in either group. Of 5 elderly men who underwent further evaluation of CH secretory ability, 2 subjects had CH levels> 10 ng/ml, either basally or after intravenous CHRH. The remaining 3 had an initially impaired CH response to bolus intravenous GHRH. After" 100 pg CHRH subcutaneously twice daily for up to 2 weeks the GH responses to intravenous bolus CHRH (0.5 flg/kg) were reassessed. One exhibited a normal response (> 10 ng/ml) after 1 week of daily CHRH treatment, another had a nearnormal response after 2 weeks (9.7 ng/ml), while the third still had an impaired response by the end of the 2-week treatment period (3.2 ng/ml).
Conclusions. The restoration of endogenous CH secretion in thes~ elderly subjects by means of GHRH priming, and the failure of manipulation of somatostatinergic tone to restore a normal CH response to CHRH suggests that somatotroph atrophy due to a reduction in endogenous CHRH secretion is the principal cause of the diminished CH secretion with ageing.
