Further evidence of cholinergic impairment of the neuroendocrinecontrol of the GH secretion in Down's syndrome
L. Beccaria
Bok Engelsk 1998
| Utgitt | 1998
|
|---|---|
| Omfang | Side 78- 81
|
| Opplysninger | There are data indicating that cholinergic activity is precociouslyimpaired in Down's syndrome (DS). On the other hand, acetylcholine aswell as arginine (ARG) play a major stimulatory role in the neuralcontrol of growth hormone (GH) secretion in humans, likely acting viathe inhibition of hypothalamic somatostatin release. The aim of thepresent study was to verify the effects of pyridostigmine (PD, 120 mgp.o.), a cholinesterase inhibitor, and ARG (0.5 g/kg i.v,) on thegrowth hormone-releasing hormone (GHRH) (1 mu g/kg i.v.)-induced GHrise in 15 adult patients with DS (M/F: 8/7; age 26.5 +/- 2.2 years,body mass index, BMI: 25.7 +/- 1.0 kg/m(2)) in which the potentiatingeffect of PD on GH secretion has been reported to be reduced. Theresults in DS were compared to those in 15 normal subjects (NS) (M/F:8/7; age: 30.0 +/- 1.3 years; BMI: 21.4 +/- 0.4 kg/m(2)). Basal GHand insulin growth factor I (IGF-1) levels in DS (1.8 +/- 0.7 and206.5 +/- 21.0 mu g/l) were similar to those in NS (1.4 +/- 0.3 and179.4 +/- 11.0 mu g/l). The GPI response to GHRH alone in DS (526.5+/- 120.1 mu g/l/h) was lon er (p < 0.05) than that recorded in NS(895.4 +/- 153.7 mu g/l/h). The GHRH-induced GH rise was potentiatedby PD both in DS (1.138 +/- 184.2 mu g/l/h; p < 0.02 vs. GHRH alone)and in NS (2.213.8 +/- 212.8 mu g/l/h p < 0.005 vs, GHRH alone),however, as the percent potentiating effect of PD was similar in bothgroups (215 and 247%, respectively) the GH response to GHRH+PD in DSwas lower (p < 0.005) than that in NS. The GHRH-induced GH rise wasalso potentiated by ARG in both DS (2,243 +/- 362.4 mu g/h: p < 0.001vs, GHRH alone) and NS (2,764.3 +/- 325.7 mu g/l/h, p < 0.005 vs.GHRH alone), As the percent potentiating effect of ARG in DS was moremarked than in NS (425 vs, 308%, respectively), the GH response toGHRH+ARG became similar in both groups, No sex-related difference wasfound in the GH response to various stimuli both in DS and NS, Inconclusion, these data demonstrate that the potentiating effect of PDbut not that of ARG is impaired in adults with DS in whom a reducedsomato-trope responsiveness to GHRH is present. These findingsindicate that in DS the pituitary GPI releasable pool is fullypreserved while an impairment of the tuberoinfundibular cholinergicpathways could lead to somatostatinergic hyperactivity and lowsomatotrope responsiveness to GHRH.
|
| Emner |
